U.S. patent application number 11/740845 was filed with the patent office on 2008-03-13 for pyrazole-amides and -sulfonamides.
This patent application is currently assigned to Icagen, Inc.. Invention is credited to Robert N. Atkinson, Michael F. Gross.
Application Number | 20080064690 11/740845 |
Document ID | / |
Family ID | 23313962 |
Filed Date | 2008-03-13 |
United States Patent
Application |
20080064690 |
Kind Code |
A1 |
Atkinson; Robert N. ; et
al. |
March 13, 2008 |
PYRAZOLE-AMIDES AND -SULFONAMIDES
Abstract
Compounds, compositions and methods are provided which are
useful in the treatment of diseases through the inhibition of
sodium ion flux through voltage-dependent sodium channels. More
particularly, the invention provides pyrazole-amides and
-sulfonamides, compositions and methods that are useful in the
treatment of central or peripheral nervous system disorders,
particularly pain and chronic pain by blocking sodium channels
associated with the onset or recurrance of the indicated
conditions. The compounds, compositions and methods of the present
invention are of particular use for treating neuropathic or
inflammatory pain by the inhibition of ion flux through a channel
that includes a PN3 subunit.
Inventors: |
Atkinson; Robert N.;
(Raleigh, NC) ; Gross; Michael F.; (Durham,
NC) |
Correspondence
Address: |
TOWNSEND AND TOWNSEND AND CREW, LLP
TWO EMBARCADERO CENTER
EIGHTH FLOOR
SAN FRANCISCO
CA
94111-3834
US
|
Assignee: |
Icagen, Inc.
Research Triangle Park
NC
|
Family ID: |
23313962 |
Appl. No.: |
11/740845 |
Filed: |
April 26, 2007 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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10286304 |
Nov 1, 2002 |
7223782 |
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11740845 |
Apr 26, 2007 |
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60335958 |
Nov 1, 2001 |
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Current U.S.
Class: |
514/227.8 ;
435/375; 514/236.5; 514/252.05; 514/254.05; 514/255.05; 514/256;
514/307; 514/326; 514/341; 514/367; 514/394; 514/406; 514/407;
544/140; 544/238; 544/333; 544/371; 544/405; 544/60; 546/139;
546/211; 546/275.4; 548/159; 548/306.1; 548/364.1; 548/365.1;
548/371.4; 548/374.1 |
Current CPC
Class: |
C07D 417/12 20130101;
C07D 405/12 20130101; C07D 401/12 20130101; C07D 231/40 20130101;
C07D 403/12 20130101; C07D 409/12 20130101; C07D 231/14 20130101;
C07D 413/12 20130101; A61P 25/00 20180101 |
Class at
Publication: |
514/227.8 ;
435/375; 514/236.5; 514/252.05; 514/254.05; 514/255.05; 514/256;
514/307; 514/326; 514/341; 514/367; 514/394; 514/406; 514/407;
544/140; 544/238; 544/333; 544/371; 544/405; 544/060; 546/139;
546/211; 546/275.4; 548/159; 548/306.1; 548/364.1; 548/365.1;
548/371.4; 548/374.1 |
International
Class: |
A61K 31/541 20060101
A61K031/541; A61K 31/415 20060101 A61K031/415; A61K 31/4184
20060101 A61K031/4184; A61K 31/428 20060101 A61K031/428; A61K
31/4427 20060101 A61K031/4427; A61K 31/4523 20060101 A61K031/4523;
A61K 31/47 20060101 A61K031/47; C07D 213/02 20060101 C07D213/02;
C07D 221/00 20060101 C07D221/00; C12N 5/00 20060101 C12N005/00;
C07D 295/00 20060101 C07D295/00; C07D 277/62 20060101 C07D277/62;
C07D 241/10 20060101 C07D241/10; C07D 239/24 20060101 C07D239/24;
C07D 237/06 20060101 C07D237/06; C07D 235/04 20060101 C07D235/04;
C07D 231/10 20060101 C07D231/10; C07D 217/00 20060101 C07D217/00;
A61P 25/00 20060101 A61P025/00; A61K 31/496 20060101 A61K031/496;
A61K 31/497 20060101 A61K031/497; A61K 31/501 20060101 A61K031/501;
A61K 31/506 20060101 A61K031/506; A61K 31/5377 20060101
A61K031/5377 |
Claims
1. A compound having the formula: ##STR40## or a pharmaceutically
acceptable salt thereof, wherein R.sup.1 and R.sup.3 are each
members independently selected from hydrogen,
(C.sub.1-C.sub.4)alkyl, (C.sub.3-C.sub.7)cycloalkyl,
(C.sub.1-C.sub.4)haloalkyl, (C.sub.1-C.sub.6)heteroalkyl, amino,
halo, cyano, nitro, hydroxy, aryl and heteroaryl; R.sup.2 is a
member selected from hydrogen, (C.sub.1-C.sub.4)alkyl,
(C.sub.1-C.sub.7)cycloalkyl, aryl, heteroaryl,
aryl(C.sub.1-C.sub.4)alkyl, and heteroaryl(C.sub.1-C.sub.4)alkyl; Y
is a member selected from: ##STR41## wherein X is a member selected
from O, S and NR.sup.8 wherein R.sup.8 is a member selected from
the group of hydrogen, cyano, nitro, alkyl, acyl, aryl and
SO.sub.2R.sup.9 wherein R.sup.9 is a member selected from alkyl,
aryl, heteroaryl and heterocycloalkyl; R.sup.4 and R.sup.5 are each
members independently selected from hydrogen,
(C.sub.1-C.sub.10)alkyl, (C.sub.3-C.sub.7)cycloalkyl,
(C.sub.1-C.sub.8)heteroalkyl, aryl, heteroaryl,
aryl(C.sub.1-C.sub.4)alkyl, heteroaryl(C.sub.1-C.sub.4)alkyl and
(C.sub.3-C.sub.8)heterocycloalkyl with the proviso that if R.sup.4
is hydrogen, R.sup.5 is not hydrogen; and R.sup.4 and R.sup.5 taken
together with the nitrogen atom to which they are attached
optionally form a 4- to 8-membered heterocycloalkyl ring; R.sup.6
is a member selected from hydrogen, (C.sub.1-C.sub.6)alkyl, aryl,
heteroaryl, aryl(C.sub.1-C.sub.4)alkyl,
heteroaryl(C.sub.1-C.sub.4)alkyl and (C.sub.1-C.sub.6)heteroalkyl;
and R.sup.7 is a member selected from (C.sub.1-C.sub.7)alkyl,
(C.sub.3-C.sub.7)cycloalkyl, (C.sub.1-C.sub.7)alkenyl,
(C.sub.1-C.sub.6)heteroalkyl, aryl, heteroaryl,
aryl(C.sub.1-C.sub.4)alkyl, heteroaryl(C.sub.1-C.sub.4)alkyl,
amino, alkoxy, (C.sub.3-C.sub.8)heterocycloalkyl and
amino(C.sub.1-C.sub.5)alkyl, and and R.sup.6 and R.sup.7 together
with the atoms to which they are attached optionally form a 4- to
8-membered heterocycloalkyl ring.
2. The compound of claim 1 having the formula: ##STR42##
3. The compound of claim 2 wherein Y has a formula which is a
member selected from: ##STR43##
4. The compound of claim 3 wherein R.sup.1 and R.sup.3 are each
members independently selected from hydrogen,
(C.sub.1-C.sub.4)alkyl, (C.sub.3-C.sub.7)cycloalkyl,
(C.sub.1-C.sub.4)haloalkyl and (C.sub.1-C.sub.5)heteroalkyl; and X
is O.
5. The compound of claim 4 wherein R.sup.2 is a member selected
from aryl and heteroaryl.
6. The compound of claim 5 wherein R.sup.3 is hydrogen.
7. The compound according to claim 6 wherein R.sup.1 is a member
selected from hydrogen, (C.sub.1-C.sub.4)alkyl, and
(C.sub.1-C.sub.4)haloalkyl.
8. The compound according to claim 3 wherein R.sup.4 is a member
selected from heteroaryl and heterocycloalkyl; and R.sup.4 and
R.sup.5, together with the nitrogen to which they are bonded are
optionally joined to form a 4- to 8-membered heterocycloalkyl ring
system.
9. The compound according to claim 8, wherein R.sup.4 and R.sup.5
taken together with the nitrogen to which they are attached form a
member selected from: ##STR44##
10. A compound having the formula: ##STR45## or a pharmaceutically
acceptable salt thereof, wherein R.sup.1 and R.sup.3 are each
members independently selected from hydrogen,
(C.sub.1-C.sub.4)alkyl, (C.sub.3-C.sub.7)cycloalkyl,
(C.sub.1-C.sub.4)haloalkyl, (C.sub.1-C.sub.6)heteroalkyl, amino,
halo, cyano, nitro, hydroxy, aryl and heteroaryl; R.sup.2 is a
member selected from hydrogen, (C.sub.1-C.sub.4)alkyl,
(C.sub.1-C.sub.7)cycloalkyl, aryl, heteroaryl,
aryl(C.sub.1-C.sub.4)alkyl, and heteroaryl(C.sub.1-C.sub.4)alkyl; Y
is a member selected from: ##STR46## wherein X is a member selected
from O, S and NR.sup.8 wherein R.sup.8 is a member selected from
hydrogen, cyano, nitro, alkyl, acyl, aryl and SO.sub.2R.sup.9
wherein R.sup.9 is a member selected from alkyl, aryl, heteroaryl
and heterocycloalkyl; R.sup.4 has a formula which is a member
selected from: ##STR47## wherein n is an integer from 0 to 4; k is
an integer from 1 to 3; R.sup.2a and R.sup.2b are members
independently selected from hydrogen and (C.sub.1-C.sub.4)alkyl,
and R.sup.2a and R.sup.2b taken together with the carbon atom to
which they are attached optionally form a 3- to 8-membered
carbocyclic or heterocycloalkyl ring; M is a member selected from
NR.sup.10, O and S wherein R.sup.10 is a member selected from
hydrogen, (C.sub.1-C.sub.6) alkyl, (C.sub.1-C.sub.8) heteroalkyl
aryl, heteroaryl and (C.sub.3-C.sub.8) cycloalkyl; A, B, D, E and G
are independently members selected from N, N-oxide and CR.sup.11
with the proviso that at most three of A, B, D, E and G is N; and
at most one of A, B, D, E and G is N-oxide wherein R.sup.11 is a
member selected from hydrogen, halo, amino, hydroxy, cyano, nitro,
(C.sub.1-C.sub.4)alkyl, (C.sub.3-C.sub.7)cycloalkyl,
(C.sub.1-C.sub.7)heteroalkyl, aryl, heteroaryl,
(C.sub.3-C.sub.8)heterocycloalkyl, alkoxy, acyl,
--C(NR.sup.12)R.sup.13, --SO.sub.2R.sup.15,
--SO.sub.2NR.sup.13R.sup.14, --NR.sup.12SOR.sup.15,
--NR.sup.12SO.sub.2NR.sup.13R.sup.14,
--NR.sup.12C(N--CN)NR.sup.13R.sup.14,
--NR.sup.12C(N--SO.sub.2R.sup.15)NR.sup.13R.sup.14,
--NR.sup.12C(N--COR.sup.15)NR.sup.13R.sup.14,
--CONR.sup.13R.sup.14,
--NR.sup.12(C.dbd.CH--NO.sub.2)NR.sup.13R.sup.14,
--NR.sup.12CONR.sup.13R.sup.14, --NR.sup.12CO--OR.sup.15,
--OCONR.sup.13R.sup.14 and R.sup.11 and R.sup.2a taken together
with the carbon atoms to which they are attached optionally form a
4- to 8-membered heterocycloalkyl group with the proviso that A is
CR.sup.11 wherein R.sup.11a is a member selected from
(C.sub.1-C.sub.6)alkyl, (C.sub.3-C.sub.7)cycloalkyl,
(C.sub.3-C.sub.8)heterocycloalkyl, aryl and heteroaryl; R.sup.12,
R.sup.13 and R.sup.14 are members independently selected from
hydrogen, (C.sub.1-C.sub.8)alkyl, (C.sub.3-C.sub.7)cycloalkyl,
(C.sub.1-C.sub.8)heteroalkyl, aryl, heteroaryl,
(C.sub.3-C.sub.8)heterocycloalkyl, aryl(C.sub.1-C.sub.4)alkyl,
heteroaryl(C.sub.1-C.sub.4)alkyl, amino(C.sub.1-C.sub.4)alkyl and
when R.sup.13 and R.sup.14 are attached to the same nitrogen atom,
they are optionally combined to form a 5-, 6- or 7-membered ring;
R.sup.15 is a member selected from (C.sub.1-C.sub.8)alkyl,
(C.sub.3-C.sub.8)cycloalkyl, (C.sub.1-C.sub.8)heteroalkyl, aryl,
heteroaryl and (C.sub.3-C.sub.8)heterocycloalkyl; R.sup.5 is a
member selected from hydrogen and (C.sub.1-C.sub.4)alkyl; and
R.sup.5 and R.sup.11 taken together with the atoms to which that
are attached optionally form a 4- to 8-membered heterocycloalkyl
ring with the proviso that A is CR.sup.11 R.sup.6 is a member
selected from hydrogen, (C.sub.1-C.sub.6)alkyl, aryl, heteroaryl,
aryl(C.sub.1-C.sub.4)alkyl, heteroaryl(C.sub.1-C.sub.4)alkyl and
(C.sub.1-C.sub.6)heteroalkyl; and R.sup.7 is a member selected from
(C.sub.1-C.sub.7)alkyl, (C.sub.3-C.sub.7)cycloalkyl,
(C.sub.1-C.sub.7)alkenyl, (C.sub.1-C.sub.6)heteroalkyl, aryl,
heteroaryl, aryl(C.sub.1-C.sub.4)alkyl,
heteroaryl(C.sub.1-C.sub.4)alkyl, amino, alkoxy,
(C.sub.3-C.sub.8)heterocycloalkyl and amino(C.sub.1-C.sub.5)alkyl,
and R.sup.6 and R.sup.7 taken together with the atoms to which they
are attached optionally form a 4- to 8-membered heterocycloalkyl
ring.
11. The compound of claim 10 wherein R.sup.1 and R.sup.3 are each
members independently selected from hydrogen,
(C.sub.1-C.sub.4)alkyl, (C.sub.3-C.sub.7)cycloalkyl,
(C.sub.1-C.sub.4)haloalkyl and (C.sub.1-C.sub.5)heteroalkyl; and X
is O.
12. The compound of claim 11 wherein R.sup.2 is a member selected
from aryl and heteroaryl.
13. The compound of claim 11 wherein one only of A, B, C, D or E is
an N or N-oxide.
14. A compound having the formula: ##STR48## or a pharmaceutically
acceptable salt thereof, wherein R.sup.1 and R.sup.3 are each
members independently selected from hydrogen,
(C.sub.1-C.sub.4)alkyl, (C.sub.3-C.sub.7)cycloalkyl,
(C.sub.1-C.sub.4)haloalkyl, (C.sub.1-C.sub.6)heteroalkyl, amino,
halo, cyano, nitro, hydroxy, aryl and heteroaryl; R.sup.2 is a
member selected from hydrogen, (C.sub.1-C.sub.4)alkyl,
(C.sub.1-C.sub.7)cycloalkyl, aryl, heteroaryl,
aryl(C.sub.1-C.sub.4)alkyl, and heteroaryl(C.sub.1-C.sub.4)alkyl; Y
is a member selected from: ##STR49## R.sup.4 has a formula which is
a member selected from: ##STR50## wherein W is a member selected
from S, SO and SO.sub.2; n is an integer from 0 to 4; R.sup.2a and
R.sup.2b are members independently selected from hydrogen and
(C.sub.1-C.sub.4)alkyl, and R.sup.2a and R.sup.2b taken together
with the carbon atom to which they are attached optionally form a
3- to 8-membered carbocyclic or heterocycloalkyl ring; R.sup.15 is
a member selected from (C.sub.1-C.sub.4)alkyl,
(C.sub.1-C.sub.6)alkenyl, (C.sub.3-C.sub.7)cycloalkyl, aryl,
heteroaryl, (C.sub.1-C.sub.8)heteroalkyl, NR.sup.16R.sup.17 wherein
R.sup.16 and R.sup.17 are members independently selected from
hydrogen, (C.sub.1-C.sub.4)alkyl, (C.sub.1-C.sub.7)cycloalkyl,
(C.sub.1-C.sub.8)heteroalkyl, (C.sub.3-C.sub.8)heterocycloalkyl,
aryl, heteroaryl, aryl(C.sub.1-C.sub.4)alkyl,
heteroaryl(C.sub.1-C.sub.4)alkyl, amino(C.sub.1-C.sub.4)alkyl, with
the proviso that when R.sup.15 is amino W is SO.sub.2; T.sup.1,
T.sup.2, T.sup.3 and T.sup.4 are each members independently
selected from hydrogen, halo, amino, cyano, nitro,
(C.sub.1-C.sub.4)alkyl, (C.sub.3-C.sub.8)cycloalkyl,
(C.sub.1-C.sub.4)haloalkyl, alkoxy, fluoro(C.sub.1-C.sub.4)alkoxy,
(C.sub.1-C.sub.7)cycloalkyl, (C.sub.1-C.sub.7)heteroalkyl, aryl and
heteroaryl, and T.sup.1 and T.sup.2 taken together with the carbon
atoms to which they are attached optionally form a 4- to 8-membered
carbocyclic or heterocycloalkyl ring; T.sup.2 and T.sup.3 taken
together with the carbon atoms to which they are attached
optionally form a 4- to 8-membered carbocyclic or heterocycloalkyl
ring; T.sup.3 and R.sup.15 taken together with the atoms to which
they are attached optionally form a 4- to 8-membered carbocyclic or
heterocycloalkyl ring; and T.sup.4 and R.sup.15 taken together with
the atoms to which they are attached optionally form a 4-to
8-membered carbocyclic or heterocycloalkyl ring; and R.sup.5 is a
member selected from hydrogen and (C.sub.1-C.sub.4)alkyl; R.sup.5
and T.sup.1 taken together with the atoms to which they are
attached optionally form a 4- to 8-membered heterocycloalkyl ring,
and R.sup.5 and T.sup.4 taken together with the atoms to which they
are attached optionally form a 4- to 8-membered heterocycloalkyl
ring.
15. The compound of claim 14 wherein R.sup.1 and R.sup.3 are each
members independently selected from hydrogen,
(C.sub.1-C.sub.4)alkyl, (C.sub.3-C.sub.7)cycloalkyl,
(C.sub.1-C.sub.4)haloalkyl and (C.sub.1-C.sub.5)heteroalkyl; and X
is O.
16. The compound of claim 14 wherein R.sup.2 is a member selected
from aryl and heteroaryl.
17. The compound of claim 15 wherein W is SO.sub.2; and R.sup.11 is
selected from substituted or unsubstituted (C.sub.1-C.sub.4)alkyl
and NR.sup.16R.sup.17; and n is 0.
18. A method of decreasing ion flow through voltage-dependent
sodium channels in a cell, said method comprising contacting said
cell with a sodium channel-inhibiting amount of a compound
comprising a pyrazolyl moiety.
19. The method according to claim 18, wherein said cell is in a
human.
20. A method of decreasing ion flow through voltage-dependent
sodium channels in a cell, said method comprising contacting said
cell with a sodium channel-inhibiting amount of a compound of the
formula: ##STR51## or a pharmaceutically acceptable salt thereof,
wherein R.sup.1 and R.sup.3 are each members independently selected
from hydrogen, (C.sub.1-C.sub.4)alkyl, (C.sub.3-C.sub.7)cycloalkyl,
(C.sub.1-C.sub.4)haloalkyl, (C.sub.1-C.sub.6)heteroalkyl, amino,
halo, cyano, nitro, hydroxy, aryl and heteroaryl; R.sup.2 is a
member selected from hydrogen, (C.sub.1-C.sub.4)alkyl,
(C.sub.1-C.sub.7)cycloalkyl, aryl, heteroaryl,
aryl(C.sub.1-C.sub.4)alkyl, and heteroaryl(C.sub.1-C.sub.4)alkyl; Y
is a member selected from: ##STR52## wherein X is a member selected
from O, S and NR.sup.8 wherein R.sup.8 is a member selected from
the group of hydrogen, cyano, nitro, alkyl, acyl, aryl and
SO.sub.2R.sup.9 wherein R.sup.9 is a member selected from alkyl,
aryl, heteroaryl and heterocycloalkyl; R.sup.4 and R.sup.5 are each
members independently selected from hydrogen,
(C.sub.1-C.sub.10)alkyl, (C.sub.3-C.sub.7)cycloalkyl,
(C.sub.1-C.sub.8)heteroalkyl, aryl, heteroaryl,
aryl(C.sub.1-C.sub.4)alkyl, heteroaryl(C.sub.1-C.sub.4)alkyl and
(C.sub.3-C.sub.8)heterocycloalkyl with the proviso that if R.sup.4
is hydrogen, R.sup.5 is not hydrogen; and R.sup.4 and R.sup.5 taken
together with the nitrogen atom to which they are attached
optionally form a 4- to 8-membered heterocycloalkyl ring; R.sup.6
is a member selected from hydrogen, (C.sub.1-C.sub.6)alkyl, aryl,
heteroaryl, aryl(C.sub.1-C.sub.4)alkyl,
heteroaryl(C.sub.1-C.sub.4)alkyl and (C.sub.1-C.sub.6)heteroalkyl;
and R.sup.7 is a member selected from (C.sub.1-C.sub.7)alkyl,
(C.sub.3-C.sub.7)cycloalkyl, (C.sub.1-C.sub.7)alkenyl,
(C.sub.1-C.sub.6)heteroalkyl, aryl, heteroaryl,
aryl(C.sub.1-C.sub.4)alkyl, heteroaryl(C.sub.1-C.sub.4)alkyl,
amino, alkoxy, (C.sub.3-C.sub.8)heterocycloalkyl and
amino(C.sub.1-C.sub.5)alkyl, and and R.sup.6 and R.sup.7 together
with the atoms to which they are attached optionally form a 4- to
8-membered heterocycloalkyl ring.
21. A method of treating a central or peripheral nervous system
disorder or condition through inhibition of a voltage-dependent
sodium channel, said method comprising administering to a subject
in need of such treatment, an effective amount of a compound
comprising a pyrazolyl moiety.
22. The method according to claim 21, said compound having the
formula: ##STR53## or a pharmaceutically acceptable salt thereof,
wherein R.sup.1 and R.sup.3 are each members independently selected
from hydrogen, (C.sub.1-C.sub.4)alkyl, (C.sub.3-C.sub.7)cycloalkyl,
(C.sub.1-C.sub.4)haloalkyl, (C.sub.1-C.sub.6)heteroalkyl, amino,
halo, cyano, nitro, hydroxy, aryl and heteroaryl; R.sup.2 is a
member selected from hydrogen, (C.sub.1-C.sub.4)alkyl,
(C.sub.1-C.sub.7)cycloalkyl, aryl, heteroaryl,
aryl(C.sub.1-C.sub.4)alkyl, and heteroaryl(C.sub.1-C.sub.4)alkyl; Y
is a member selected from: ##STR54## wherein X is a member selected
from O, S and NR.sup.8 wherein R.sup.8 is a member selected from
the group of hydrogen, cyano, nitro, alkyl, acyl, aryl and
SO.sub.2R.sup.9 wherein R.sup.9 is a member selected from alkyl,
aryl, heteroaryl and heterocycloalkyl; R.sup.4 and R.sup.5 are each
members independently selected from hydrogen,
(C.sub.1-C.sub.10)alkyl, (C.sub.3-C.sub.7)cycloalkyl,
(C.sub.1-C.sub.8)heteroalkyl, aryl, heteroaryl,
aryl(C.sub.1-C.sub.4)alkyl, heteroaryl(C.sub.1-C.sub.4)alkyl and
(C.sub.3-C.sub.8)heterocycloalkyl with the proviso that if R.sup.4
is hydrogen, R.sup.5 is not hydrogen; and R.sup.4 and R.sup.5 taken
together with the nitrogen atom to which they are attached
optionally form a 4- to 8-membered heterocycloalkyl ring; R.sup.6
is a member selected from hydrogen, (C.sub.1-C.sub.6)alkyl, aryl,
heteroaryl, aryl(C.sub.1-C.sub.4)alkyl,
heteroaryl(C.sub.1-C.sub.4)alkyl and (C.sub.1-C.sub.6)heteroalkyl;
and R.sup.7 is a member selected from (C.sub.1-C.sub.7)alkyl,
(C.sub.3-C.sub.7)cycloalkyl, (C.sub.1-C.sub.7)alkenyl,
(C.sub.1-C.sub.6)heteroalkyl, aryl, heteroaryl,
aryl(C.sub.1-C.sub.4)alkyl, heteroaryl(C.sub.1-C.sub.4)alkyl,
amino, alkoxy, (C.sub.3-C.sub.8)heterocycloalkyl and
amino(C.sub.1-C.sub.5)alkyl, and and R.sup.6 and R.sup.7 together
with the atoms to which they are attached optionally form a 4- to
8-membered heterocycloalkyl ring.
23. The method according to claim 20, wherein said disorder is pain
selected from inflammatory pain, neuropathic pain and combinations
thereof.
24. A composition comprising a pharmaceutically acceptable
excipient and a compound having the formula: ##STR55## or a
pharmaceutically acceptable salt thereof, wherein R.sup.1 and
R.sup.3 are each members independently selected from hydrogen,
(C.sub.1-C.sub.4)alkyl, (C.sub.3-C.sub.7)cycloalkyl,
(C.sub.1-C.sub.4)haloalkyl, (C.sub.1-C.sub.6)heteroalkyl, amino,
halo, cyano, nitro, hydroxy, aryl and heteroaryl; R.sup.2 is a
member selected from hydrogen, (C.sub.1-C.sub.4)alkyl,
(C.sub.1-C.sub.7)cycloalkyl, aryl, heteroaryl,
aryl(C.sub.1-C.sub.4)alkyl, and heteroaryl(C.sub.1-C.sub.4)alkyl; Y
is a member selected from: ##STR56## wherein X is a member selected
from O, S and NR.sup.8 wherein R.sup.8 is a member selected from
the group of hydrogen, cyano, nitro, alkyl, acyl, aryl and
SO.sub.2R.sup.9 wherein R.sup.9 is a member selected from alkyl,
aryl, heteroaryl and heterocycloalkyl; R.sup.4 and R.sup.5 are each
members independently selected from hydrogen,
(C.sub.1-C.sub.10)alkyl, (C.sub.3-C.sub.7)cycloalkyl,
(C.sub.1-C.sub.8)heteroalkyl, aryl, heteroaryl,
aryl(C.sub.1-C.sub.4)alkyl, heteroaryl(C.sub.1-C.sub.4)alkyl and
(C.sub.3-C.sub.8)heterocycloalkyl with the proviso that if R.sup.4
is hydrogen, R.sup.5 is not hydrogen; and R.sup.4 and R.sup.5 taken
together with the nitrogen atom to which they are attached
optionally form a 4- to 8-membered heterocycloalkyl ring; R.sup.6
is a member selected from hydrogen, (C.sub.1-C.sub.6)alkyl, aryl,
heteroaryl, aryl(C.sub.1-C.sub.4)alkyl,
heteroaryl(C.sub.1-C.sub.4)alkyl and (C.sub.1-C.sub.6)heteroalkyl;
and R.sup.7 is a member selected from (C.sub.1-C.sub.7)alkyl,
(C.sub.3-C.sub.7)cycloalkyl, (C.sub.1-C.sub.7)alkenyl,
(C.sub.1-C.sub.6)heteroalkyl, aryl, heteroaryl,
aryl(C.sub.1-C.sub.4)alkyl, heteroaryl(C.sub.1-C.sub.4)alkyl,
amino, alkoxy, (C.sub.3-C.sub.8)heterocycloalkyl and
amino(C.sub.1-C.sub.5)alkyl, and and R.sup.6 and R.sup.7 together
with the atoms to which they are attached optionally form a 4- to
8-membered heterocycloalkyl ring.
Description
CROSS-REFERENCES TO RELATED APPLICATIONS
[0001] This is a non-provisional filing of U.S. Provisional Patent
Application No. 60/335,958, filed on Nov. 1, 2001, the disclosure
of which is incorporated herein by reference in its entirety for
all purposes.
FIELD OF THE INVENTION
[0002] This invention relates to the use of certain pyrazole amide
and pyrazole sulfonamide compounds as sodium channel inhibitors and
to the treatment of neuropathic pain by the inhibition of sodium
channels. Additionally, this invention relates to novel
pyrazole-based compounds that are useful as sodium channel
inhibitors.
BACKGROUND OF THE INVENTION
[0003] Sodium channel-blocking agents have been reported to be
effective in the treatment of various disease states, and have
found particular use as local anesthetics and in the treatment of
cardiac arrhythmias. It has also been reported that sodium
channel-blocking agents may also be useful in the treatment of
pain, including neuropathic pain; see, for example, Tanelian et al.
Pain Forum. 4(2), 75-80 (1995). Preclinical evidence demonstrates
that sodium channel-blocking agents selectively suppress abnormal
ectopic neural firing in injured peripheral and central neurons,
and it is via this mechanism that they are believed to be useful
for relieving pain. Consistent with this hypothesis, it has been
shown that sodium channels accumulate in the peripheral nerve at
sites of axonal injury (Devor et al. J. Neurosci. 132: 1976
(1993)). Alterations in either the level of expression or
distribution of sodium channels within an injured nerve, therefore,
have a major influence on the pathophysiology of pain associated
with this type of trauma.
[0004] An increasing body of evidence suggests that a
voltage-dependent, tetrodotoxin (TTX)-resistant Na channel, PN3
(Na.sub.v1.8), may play a key role in sensitization in neuropathic
pain states. Neuropathic pain can be described as pain associated
with damage or permanent alteration of the peripheral or central
nervous system. Clinical manifestations of neuropathic pain include
a sensation of burning or electric shock, feelings of bodily
distortion, allodynia and hyperalgesia.
[0005] PN3 is a member of a family of voltage-gated sodium channel
alpha subunits. Names for this family include SCN, SCNA, and
Na.sub.vx.x. There are currently 10 known members falling into two
subfamilies Na.sub.v1 (all but SCN6A) and Na.sub.v2 (SCN6A). The
human channel was cloned by Rabert et al. (Pain 78(2): 107-114
(1998)). PN3 of other species has also been cloned. See, for
example, Chen et al., Gene 202(1-2), 7-14 (1997); Souslova et al.,
Genomics 41(2), 201-209 (1997); Akopian et al., Nature 379(6562),
257-262 (1996).
[0006] PN3-null mutant mice exhibit a pronounced analgesia to
mechanical noxious stimuli (Akopian A. N. et al., Nature Neurosci.,
2(6): 541-548 (1999)). Selective "knock down" of PN3 protein in the
rat dorsal root ganglion with specific antisense
oligodeoxynucleotides prevents hyperalgesia and allodynia caused by
either chronic nerve or tissue injury (Porreca et al., Proc. Nat.
Acad. Sci., USA, 96: 7640-7644 (1999)). The biophysical properties
of PN3 make it ideally suited to sustain repetitive firing of
sensory neurons at the depolarized potentials characteristic of
injured peripheral nerves. In both human and animal models of
neuropathic pain, there is an increased expression of PN3 at the
site of peripheral nerve injury (Clare et al., DDT 5: 506-519
(2000); Coward et al., Pain 85: 41-50 (2000)).
[0007] Patients with neuropathic pain do not respond to
non-steroidal anti-inflammatory drugs (NSAIDS) and resistance or
insensitivity to opiates is common. Most other treatments have
limited efficacy or undesirable side effects. Mannion et al.,
Lancet, 353: 1959-1964 (1999) from the Department of Anesthesia and
Critical Care, Massachusetts General Hospital and Harvard Medical
School wrote: "There is no treatment to prevent the development of
neuropathic pain, nor to adequately, predictably and specifically
control established neuropathic pain."
[0008] PN3 is a promising molecular target for the treatment of
neuropathic pain. One of the most attractive features of PN3 is the
highly restricted and peripheral nature of its expression.
Antisense studies have revealed no overt (particularly CNS-related)
adverse effects, consistent with the localized, peripheral
distribution of the channel (Novakovic et al., J. Neurosci., 18(6):
2174-2187 (1998)). Additionally, the high activation threshold of
PN3 suggests that the channel may be relatively uninvolved in
normal nociception. These properties of PN3 present the possibility
that selective blockade of this particular voltage-gated sodium
channel (VGSC) may offer effective pain relief without the
significant side effect liability normally associated with more
promiscuous VGSC blocking drugs. The compounds of the invention are
potent inhibitors of PN3 channels.
[0009] Ohkawa et al. have described a class of cyclic ethers that
are of use as sodium channel blockers (U.S. Pat. No.
6,172,085).
[0010] Currently, gabapentin is the market leading treatment for
neuropathic pain. As with epilepsy, its mechanism of action for
pain is unknown. It is a very safe, easy to use drug, which
contributes to its sales. Efficacy for neuropathic pain is not
impressive, as few as only 30% of patients respond to gabapentin
treatment. Carbamazepine is also used to treat neuropathic
pain.
[0011] In view of the limited number of agents presently available
and the low levels of efficacy of the available agents, there is a
pressing need for compounds that are potent, specific inhibitors of
ion channels implicated in neuropathic pain. The present invention
provides such compounds, methods of using them, and compositions
that include the compounds.
SUMMARY OF THE INVENTION
[0012] It has now been discovered that pyrazole-amides and
-sulfonamides are potent inhibitors of sodium channels. In the
discussion that follows, the invention is exemplified by reference
to the inhibition of sodium channels that are localized in the
peripheral nervous system, and in particular those inhibitors that
are selective inhibitors of PN3, and are useful for treating
neuropathic pain through the inhibition of sodium ion flux through
channels that include the PN3 subunit. The focus of the discussion
is for clarity of illustration only.
[0013] The compounds and methods of the present invention are
useful for treating diseases in which blocking or inhibiting one or
more PN3 ion channel provides relief from the disease. Of
particular interest is the use of the compounds and methods of the
invention for treating pain and central or peripheral nervous
system disorders. The present invention is of use for treating both
inflammatory and neuropathic pain.
[0014] The present invention provides compounds which are useful in
the treatment of diseases through the inhibition of sodium ion flux
through voltage-dependent sodium channels. More particularly, the
invention provides compounds, compositions and methods that are
useful in the treatment of central or peripheral nervous system
disorders, particularly pain and chronic pain.
[0015] In one aspect, the present invention provides compounds
according to Formula I: ##STR1## or a pharmaceutically acceptable
salt thereof. In Formula I, the symbols R.sup.1 and R.sup.3 are
independently selected from hydrogen, (C.sub.1-C.sub.4)alkyl,
(C.sub.3-C.sub.7)cycloalkyl, (C.sub.1-C.sub.4)haloalkyl,
(C.sub.1-C.sub.6)heteroalkyl, amino, halo, cyano, nitro, hydroxy,
aryl and heteroaryl. The symbol R.sup.2 represents hydrogen,
(C.sub.1-C.sub.4)alkyl, (C.sub.1-C.sub.7)cycloalkyl, aryl,
heteroaryl, aryl(C.sub.1-C.sub.4)alkyl, or
heteroaryl(C.sub.1-C.sub.4)alkyl;
[0016] The symbol Y is a member selected from: ##STR2## wherein X
is a member selected from O, S and NR.sup.8. The symbol R.sup.8
represents hydrogen, cyano, nitro, alkyl, acyl, aryl or
SO.sub.2R.sup.9. R.sup.9 is selected from alkyl, aryl, heteroaryl
and heterocycloalkyl. The symbols R.sup.4 and R.sup.5 independently
represent hydrogen, (C.sub.1-C.sub.10)alkyl,
(C.sub.3-C.sub.7)cycloalkyl, (C.sub.1-C.sub.8)heteroalkyl, aryl,
heteroaryl, aryl(C.sub.1-C.sub.4)alkyl,
heteroaryl(C.sub.1-C.sub.4)alkyl and
(C.sub.3-C.sub.8)heterocycloalkyl, with the proviso that if R.sup.4
is hydrogen, R.sup.5 is not hydrogen. R.sup.4 and R.sup.5 taken
together with the nitrogen atom to which they are attached
optionally form a 4- to 8-membered heterocycloalkyl ring. The
symbol R.sup.6 represents hydrogen, (C.sub.1-C.sub.6)alkyl, aryl,
heteroaryl, aryl(C.sub.1-C.sub.4)alkyl,
heteroaryl(C.sub.1-C.sub.4)alkyl or (C.sub.1-C.sub.6)heteroalkyl.
R.sup.7 is selected from (C.sub.1-C.sub.7)alkyl,
(C.sub.3-C.sub.7)cycloalkyl, (C.sub.1-C.sub.7)alkenyl,
(C.sub.1-C.sub.6)heteroalkyl, aryl, heteroaryl,
aryl(C.sub.1-C.sub.4)alkyl, heteroaryl(C.sub.1-C.sub.4)alkyl,
amino, alkoxy, (C.sub.3-C.sub.8)heterocycloalkyl and
amino(C.sub.1-C.sub.5)alkyl, and and R.sup.6 and R.sup.7 together
with the atoms to which they are attached optionally form a 4- to
8-membered heterocycloalkyl ring.
[0017] In another aspect, the present invention provides
pharmaceutical compositions comprising a pharmaceutically
acceptable excipient and a compound provided above.
[0018] In yet another aspect, the present invention provides a
method for inhibiting ion flux through voltage dependent sodium
channels, comprising contacting a cell containing the target ion
channels with a compound that comprises a pyrazolyl moiety, such as
the compounds of Formula I.
[0019] In still another aspect, the present invention provides a
method for the treatment of diseases through inhibition of ion flux
through voltage dependent sodium channels, the method comprising
treating the host with an effective amount of a sodium channel
inhibiting compound comprising a pyrazolyl moiety, such as a
compound of Formula I.
[0020] Other objects, advantages and embodiments of the invention
will be apparent from review of the detailed description that
follows.
BRIEF DESCRIPTION OF THE DRAWINGS
[0021] FIG. 1 is a table displaying structures of representative
compounds of the invention.
DETAILED DESCRIPTION OF THE INVENTION AND THE PREFERRED
EMBODIMENTS
Definitions
[0022] The term "pain" refers to all categories of pain, including
pain that is described in terms of stimulus or nerve response,
e.g., somatic pain (normal nerve response to a noxious stimulus)
and neuropathic pain (abnormal response of a injured or altered
sensory pathway, often without clear noxious input); pain that is
categorized temporally, e.g., chronic pain and acute pain; pain
that is categorized in terms of its severity, e.g., mild, moderate,
or severe; and pain that is a symptom or a result of a disease
state or syndrome, e.g., inflammatory pain, cancer pain, AIDS pain,
arthropathy, migraine, trigeminal neuralgia, cardiac ischaemia, and
diabetic neuropathy (see, e.g., Harrison's Principles of Internal
Medicine, pp. 93-98 (Wilson et al., eds., 12th ed. 1991); Williams
et al., J. of Medicinal Chem. 42:1481-1485 (1999), herein each
incorporated by reference in their entirety).
[0023] "Somatic" pain, as described above, refers to a normal nerve
response to a noxious stimulus such as injury or illness, e.g.,
trauma, burn, infection, inflammation, or disease process such as
cancer, and includes both cutaneous pain (e.g., skin, muscle or
joint derived) and visceral pain (e.g., organ derived).
[0024] "Neuropathic" pain, as described above, refers to pain
resulting from injury to or chronic changes in peripheral and/or
central sensory pathways, where the pain often occurs or persists
without an obvious noxious input.
[0025] "Biological medium," as used herein refers to both in vitro
and in vivo biological milieus. Exemplary in vitro "biological
media" include, but are not limited to, cell culture, tissue
culture, homogenates, plasma and blood. In vivo applications are
generally performed in mammals, preferably humans.
[0026] "Compound of the invention," as used herein refers to the
compounds discussed herein, pharmaceutically acceptable salts and
prodrugs of these compounds.
[0027] "Inhibiting" and "blocking," are used interchangeably herein
to refer to the partial or full blockade of a PN3 channel by a
compound of the invention, which leads to a decrease in ion flux
either into or out of a cell in which a PN3 channel is found.
[0028] Where substituent groups are specified by their conventional
chemical formulae, written from left to right, they equally
encompass the chemically identical substituents which would result
from writing the structure from right to left, e.g., --CH.sub.2O--
is intended to also recite --OCH.sub.2--; --NHS(O).sub.2-- is also
intended to represent. --S(O).sub.2HN--, etc.
[0029] The term "alkyl," by itself or as part of another
substituent, means, unless otherwise stated, a straight or branched
chain, or cyclic hydrocarbon radical, or combination thereof, which
may be fully saturated, mono- or polyunsaturated and can include
di- and multivalent radicals, having the number of carbon atoms
designated (i.e. C.sub.1-C.sub.10 means one to ten carbons).
Examples of saturated hydrocarbon radicals include, but are not
limited to, groups such as methyl, ethyl, n-propyl, isopropyl,
n-butyl, t-butyl, isobutyl, sec-butyl, cyclohexyl,
(cyclohexyl)methyl, cyclopropylmethyl, homologs and isomers of, for
example, n-pentyl, n-hexyl, n-heptyl, n-octyl, and the like. An
unsaturated alkyl group is one having one or more double bonds or
triple bonds. Examples of unsaturated alkyl groups include, but are
not limited to, vinyl, 2-propenyl, crotyl, 2-isopentenyl,
2-(butadienyl), 2,4-pentadienyl, 3-(1,4-pentadienyl), ethynyl, 1-
and 3-propynyl, 3-butynyl, and the higher homologs and isomers. The
term "alkyl," unless otherwise noted, is also meant to include
those derivatives of alkyl defined in more detail below, such as
"heteroalkyl." Alkyl groups, which are limited to hydrocarbon
groups are termed "homoalkyl".
[0030] The term "alkylene" by itself or as part of another
substituent means a divalent radical derived from an alkane, as
exemplified, but not limited, by
--CH.sub.2CH.sub.2CH.sub.2CH.sub.2--, and further includes those
groups described below as "heteroalkylene." Typically, an alkyl (or
alkylene) group will have from 1 to 24 carbon atoms, with those
groups having 10 or fewer carbon atoms being preferred in the
present invention. A "lower alkyl" or "lower alkylene" is a shorter
chain alkyl or alkylene group, generally having eight or fewer
carbon atoms.
[0031] The terms "alkoxy," "alkylamino" and "alkylthio" (or
thioalkoxy) are used in their conventional sense, and refer to
those alkyl groups attached to the remainder of the molecule via an
oxygen atom, an amino group, or a sulfur atom, respectively.
[0032] The term "amino" refers to --NRR' in which R and R' are
members independently selected from H, substituted or unsubstituted
alkyl, substituted or unsubstituted heteroalkyl, substituted or
unsubstituted aryl, substituted or unsubstituted heteroaryl and
substituted or unsubstituted heterocycloalkyl.
[0033] The term "heteroalkyl," by itself or in combination with
another term, means, unless otherwise stated, a stable straight or
branched chain, or cyclic hydrocarbon radical, or combinations
thereof, consisting of the stated number of carbon atoms and at
least one heteroatom selected from O, N, Si and S, and wherein the
nitrogen and sulfur atoms may optionally be oxidized and the
nitrogen heteroatom may optionally be quaternized. The
heteroatom(s) O, N and S and Si may be placed at any interior
position of the heteroalkyl group or at the position at which the
alkyl group is attached to the remainder of the molecule. Examples
include, but are not limited to, --CH.sub.2--CH.sub.2--O--CH.sub.3,
--CH.sub.2--CH.sub.2--NH--CH.sub.3,
--CH.sub.2--CH.sub.2--N(CH.sub.3)--CH.sub.3,
--CH.sub.2--S--CH.sub.2--CH.sub.3,
--CH.sub.2--CH.sub.2,--S(O)--CH.sub.3,
--CH.sub.2--CH.sub.2--S(O).sub.2--CH.sub.3,
--CH.dbd.CH--O--CH.sub.3, --Si(CH.sub.3).sub.3,
--CH.sub.2--CH.dbd.N--OCH.sub.3, and
--CH.dbd.CH--N(CH.sub.3)--CH.sub.3. Up to two heteroatoms may be
consecutive, such as, for example, --CH.sub.2--NH--OCH.sub.3 and
--CH.sub.2--O--Si(CH.sub.3).sub.3. Similarly, the term
"heteroalkylene" by itself or as part of another substituent means
a divalent radical derived from heteroalkyl, as exemplified, but
not limited by, --CH.sub.2--CH.sub.2--S--CH.sub.2--CH.sub.2-- and
--CH.sub.2--S--CH.sub.2--CH.sub.2--NH--CH.sub.2--. For
heteroalkylene groups, heteroatoms can also occupy either or both
of the chain termini (e.g., alkyleneoxy, alkylenedioxy,
alkyleneamino, alkylenediamino, and the like). Still further, for
alkylene and heteroalkylene linking groups, no orientation of the
linking group is implied by the direction in which the formula of
the linking group is written. For example, the formula
--C(O).sub.2R'-- represents both --C(O).sub.2R'-- and
--R'C(O).sub.2--.
[0034] In general, an "acyl" or "acyl substituent" is also selected
from the group set forth above. As used herein, the term "acyl
substituent" refers to groups attached to, and fulfilling the
valence of a carbonyl carbon that is either directly or indirectly
attached to the nucleus of the compounds of the present
invention.
[0035] The terms "cycloalkyl" and "heterocycloalkyl", by themselves
or in combination with other terms, represent, unless otherwise
stated, cyclic versions of "alkyl" and "heteroalkyl", respectively.
Additionally, for heterocycloalkyl, a heteroatom can occupy the
position at which the heterocycle is attached to the remainder of
the molecule. Examples of cycloalkyl include, but are not limited
to, cyclopropyl, cyclopentyl, cyclohexyl, 1-cyclohexenyl,
3-cyclohexenyl, cycloheptyl, and the like. Examples of
heterocycloalkyl include, but are not limited to,
1-(1,2,5,6-tetrahydropyridyl), 1-piperidinyl, 2-piperidinyl,
3-piperidinyl, 4-morpholinyl, 3-morpholinyl, tetrahydrofuran-2-yl,
tetrahydrofuran-3-yl, tetrahydrothien-2-yl, tetrahydrothien-3-yl,
1-piperazinyl, 2-piperazinyl, 1-pyrrolidine, 2-pyrrolidine,
3-pyrrolidine and the like.
[0036] The terms "halo" or "halogen," by themselves or as part of
another substituent, mean, unless otherwise stated, a fluorine,
chlorine, bromine, or iodine atom. Additionally, terms such as
"haloalkyl," are meant to include monohaloalkyl and polyhaloalkyl.
For example, the term "halo(C.sub.1-C.sub.4)alkyl" is meant to
include, but not be limited to, trifluoromethyl,
2,2,2-trifluoroethyl, 4-chlorobutyl, 3-bromopropyl, and the
like.
[0037] The term "aryl" means, unless otherwise stated, a
polyunsaturated, aromatic, hydrocarbon substituent which can be a
single ring or multiple rings (preferably from 1 to 3 rings) which
are fused together or linked covalently. The term "heteroaryl"
refers to aryl groups (or rings) that contain from one to four
heteroatoms selected from N, O, and S, wherein the nitrogen and
sulfur atoms are optionally oxidized, and the nitrogen atom(s) are
optionally quaternized. A heteroaryl group can be attached to the
remainder of the molecule through a heteroatom. Non-limiting
examples of aryl and heteroaryl groups include phenyl, 1-naphthyl,
2-naphthyl, 4-biphenyl, 1-pyrrolyl, 2-pyrrolyl, 3-pyrrolyl,
1-pyrazole, 3-pyrazolyl, 4-pyrazole, 5-pyrazole, 2-imidazolyl,
4-imidazolyl, pyrazinyl, 2-oxazolyl, 4-oxazolyl,
2-phenyl-4-oxazolyl, 5-oxazolyl, 3-isoxazolyl, 4-isoxazolyl,
5-isoxazolyl, 2-thiazolyl, 4-thiazolyl, 5-thiazolyl, 2-furyl,
3-furyl, 2-thienyl, 3-thienyl, 2-pyridyl, 3-pyridyl, 4-pyridyl,
2-pyrimidyl, 4-pyrimidyl, 5-benzothiazolyl, purinyl,
2-benzimidazolyl, 2-benzthiazole, 2-benzoxazole, 5-indolyl,
1-isoquinolyl, 5-isoquinolyl, 2-quinoxalinyl, 5-quinoxalinyl,
3-quinolyl, and 6-quinolyl. Substituents for each of the above
noted aryl and heteroaryl ring systems are selected from the group
of acceptable substituents described below.
[0038] For brevity, the term "aryl" when used in combination with
other terms (e.g., aryloxy, arylthioxy, arylalkyl) includes both
aryl and heteroaryl rings as defined above. Thus, the term
"arylalkyl" is meant to include those radicals in which an aryl
group is attached to an alkyl group (e.g., benzyl, phenethyl,
pyridylmethyl and the like) including those alkyl groups in which a
carbon atom (e.g., a methylene group) has been replaced by, for
example, an oxygen atom (e.g., phenoxymethyl, 2-pyridyloxymethyl,
3-(1-naphthyloxy)propyl, and the like).
[0039] Each of the above terms (e.g., "alkyl," "heteroalkyl,"
"aryl" and "heteroaryl") include both substituted and unsubstituted
forms of the indicated radical. Preferred substituents for each
type of radical are provided below.
[0040] Substituents for the alkyl, and heteroalkyl radicals
(including those groups often referred to as alkylene, alkenyl,
heteroalkylene, heteroalkenyl, alkynyl, cycloalkyl,
heterocycloalkyl, cycloalkenyl, and heterocycloalkenyl) are
generally referred to as "alkyl substituents" and "heteroalkyl
substituents," respectively, and they can be one or more of a
variety of groups selected from, but not limited to: -hydrogen,
--OR', .dbd.O, .dbd.NR'''', .dbd.N--OR', --NR'R'', --SR', -halogen,
--SiR'R''R''', --OC(O)R', --C(O)R', --CO.sub.2R', --CONR'R'',
--OC(O)NR'R'', --NR'C(O)R'', --NR'''--C(O)NR'R'',
--NR'C(O).sub.2R'', --NR'''--C(NR'R'').dbd.NR'''',
--NR'''--C(NR'R'').dbd.NR'''', --S(O)R', --S(O).sub.2R',
--S(O).sub.2NR'R'', --NR'SO.sub.2R'', --NR'''SO.sub.2NR'R''--CN,
--R' and --NO.sub.2 in a number ranging from zero to (2m'+1), where
m' is the total number of carbon atoms in such radical. R', R'',
R''' each preferably independently refer to hydrogen, substituted
or unsubstituted alkyl, substituted or unsubstituted heteroalkyl,
substituted or unsubstituted aryl, (e.g., aryl substituted with 1-3
halogens, substituted or unsubstituted alkyl, alkoxy or thioalkoxy
groups), substituted or unsubstituted heteroaryl and substituted or
unsubstituted arylalkyl. R'''' refers to hydrogen, alkyl,
substituted or unsubstituted heteroalkyl, substituted or
unsubstituted aryl, substituted or unsubstituted heteroaryl,
substituted or unsubstituted arylalkyl, --CN, --NO.sub.2 and
--S(O).sub.2R'. When a compound of the invention includes more than
one R group, for example, each of the R groups is independently
selected as are each R', R'', R''' and R'''' groups when more than
one of these groups is present. When R' and R'' are attached to the
same nitrogen atom, they can be combined with the nitrogen atom to
form a 5-, 6-, or 7-membered ring. For example, --NR'R'' is meant
to include, but not be limited to, 1-pyrrolidinyl, 1-piperidinyl,
1-piperazinyl and 4-morpholinyl. From the above discussion of
substituents, one of skill in the art will understand that the term
"alkyl" is meant to include groups including carbon atoms bound to
groups other than hydrogen groups, such as haloalkyl (e.g.,
--CF.sub.3 and --CH.sub.2CF.sub.3) and acyl (e.g., --C(O)CH.sub.3,
--C(O)CF.sub.3, --C(O)CH.sub.2OCH.sub.3, and the like).
[0041] Similar to the substituents described for the alkyl radical,
the aryl substituents and heteroaryl substituents are generally
referred to as "aryl substituents" and "heteroaryl substituents,"
respectively and are varied and selected from, for example:
hydrogen, --OR', --C.dbd.NR''''NR'R'', --NR'''SO.sub.2NR'R'',
--NR'R'', --SR', -halogen, --SiR'R''R''', --OC(O)R', --C(O)R',
--CO.sub.2R', --CONR'R'', --OC(O)NR'R'', --NR''C(O)R',
--NR'''--C(O)NR'R'', --NR''C(O).sub.2R',
--NR'''--C(NR'R'').dbd.NR'''', --S(O)R', --S(O).sub.2R',
--S(O).sub.2NR'R'', --NR''SO.sub.2R', --CN and --NO.sub.2, --R',
--N.sub.3, --CH(Ph).sub.2, fluoro(C.sub.1-C.sub.4)alkoxy, and
fluoro(C.sub.1-C.sub.4)alkyl, in a number ranging from zero to the
total number of open valences on the aromatic ring system; and
where R', R'' and R''' each preferably independently refer to
hydrogen, substituted or unsubstituted alkyl, substituted or
unsubstituted heteroalkyl, substituted or unsubstituted aryl,
(e.g., aryl substituted with 1-3 halogens, substituted or
unsubstituted alkyl, alkoxy or thioalkoxy groups), substituted or
unsubstituted heteroaryl and substituted or unsubstituted
arylalkyl. R'''' refers to hydrogen, alkyl, substituted or
unsubstituted heteroalkyl, substituted or unsubstituted aryl,
substituted or unsubstituted heteroaryl, substituted or
unsubstituted arylalkyl, --CN, --NO.sub.2 and --S(O).sub.2R'. When
a compound of the invention includes more than one R group, for
example, each of the R groups is independently selected as are each
R', R'', R''' and R'''' groups when more than one of these groups
is present. When R' and R'' are attached to the same nitrogen atom,
they can be combined with the nitrogen atom to form a 5-, 6-, or
7-membered ring. For example, --NR'R'' is meant to include, but not
be limited to, 1-pyrrolidinyl, 1-piperidinyl, 1-piperazinyl and
4-morpholinyl.
[0042] Two of the aryl substituents on adjacent atoms of the aryl
or heteroaryl ring may optionally be replaced with a substituent of
the formula -T-C(O)--(CRR').sub.q-U-, wherein T and U are
independently --NR--, --O--, --CRR'-- or a single bond, and q is an
integer of from 0 to 3. Alternatively, two of the substituents on
adjacent atoms of the aryl or heteroaryl ring may optionally be
replaced with a substituent of the formula -A-(CH.sub.2).sub.r-B-,
wherein A and B are independently --CRR'--, --O--, --NR--, --S--,
--S(O)--, --S(O).sub.2--, --S(O).sub.2NR'-- or a single bond, and r
is an integer of from 1 to 4. One of the single bonds of the new
ring so formed may optionally be replaced with a double bond.
Alternatively, two of the substituents on adjacent atoms of the
aryl or heteroaryl ring may optionally be replaced with a
substituent of the formula --(CRR').sub.s--X--(CR''R''').sub.d--,
where s and d are independently integers of from 0 to 3, and X is
--O--, --NR'--, --S--, --S(O)--, --S(O).sub.2--, or
--S(O).sub.2NR'--. The substituents R, R', R'' and R''' are
preferably independently selected from hydrogen or substituted or
unsubstituted (C.sub.1-C.sub.6)alkyl.
[0043] As used herein, the term "heteroatom" includes oxygen (O),
nitrogen (N), sulfur (S) and silicon (Si).
[0044] The symbol "R" is a general abbreviation that represents a
substituent group that is selected from hydrogen, substituted or
unsubstituted alkyl, substituted or unsubstituted heteroalkyl,
substituted or unsubstituted aryl, substituted or unsubstituted
heteroaryl, and substituted or unsubstituted heterocyclyl
groups.
[0045] The symbol , whether utilized as a bond or displayed
perpendicular to a bond indicates the point at which the displayed
moiety is attached to the remainder of the molecule, solid support,
etc.
[0046] The term "pharmaceutically acceptable salts" includes salts
of the active compounds which are prepared with relatively nontoxic
acids or bases, depending on the particular substituents found on
the compounds described herein. When compounds of the present
invention contain relatively acidic functionalities, base addition
salts can be obtained by contacting the neutral form of such
compounds with a sufficient amount of the desired base, either neat
or in a suitable inert solvent. Examples of pharmaceutically
acceptable base addition salts include sodium, potassium, calcium,
ammonium, organic amino, or magnesium salt, or a similar salt. When
compounds of the present invention contain relatively basic
functionalities, acid addition salts can be obtained by contacting
the neutral form of such compounds with a sufficient amount of the
desired acid, either neat or in a suitable inert solvent. Examples
of pharmaceutically acceptable acid addition salts include those
derived from inorganic acids like hydrochloric, hydrobromic,
nitric, carbonic, monohydrogencarbonic, phosphoric,
monohydrogenphosphoric, dihydrogenphosphoric, sulfuric,
monohydrogensulfuric, hydriodic, or phosphorous acids and the like,
as well as the salts derived from relatively nontoxic organic acids
like acetic, propionic, isobutyric, maleic, malonic, benzoic,
succinic, suberic, fumaric, lactic, mandelic, phthalic,
benzenesulfonic, p-tolylsulfonic, citric, tartaric,
methanesulfonic, and the like. Also included are salts of amino
acids such as arginate and the like, and salts of organic acids
like glucuronic or galactunoric acids and the like (see, for
example, Berge et al., "Pharmaceutical Salts", Journal of
Pharmaceutical Science, 1977, 66, 1-19). Certain specific compounds
of the present invention contain both basic and acidic
functionalities that allow the compounds to be converted into
either base or acid addition salts.
[0047] The neutral forms of the compounds are preferably
regenerated by contacting the salt with a base or acid and
isolating the parent compound in the conventional manner. The
parent form of the compound differs from the various salt forms in
certain physical properties, such as solubility in polar solvents,
but otherwise the salts are equivalent to the parent form of the
compound for the purposes of the present invention.
[0048] In addition to salt forms, the present invention provides
compounds, which are in a prodrug form. Prodrugs of the compounds
described herein are those compounds that readily undergo chemical
changes under physiological conditions to provide the compounds of
the present invention. Additionally, prodrugs can be converted to
the compounds of the present invention by chemical or biochemical
methods in an ex vivo environment. For example, prodrugs can be
slowly converted to the compounds of the present invention when
placed in a transdermal patch reservoir with a suitable enzyme or
chemical reagent.
[0049] Certain compounds of the present invention can exist in
unsolvated forms as well as solvated forms, including hydrated
forms. In general, the solvated forms are equivalent to unsolvated
forms and are encompassed within the scope of the present
invention. Certain compounds of the present invention may exist in
multiple crystalline or amorphous forms. In general, all physical
forms are equivalent for the uses contemplated by the present
invention and are intended to be within the scope of the present
invention.
[0050] Certain compounds of the present invention possess
asymmetric carbon atoms (optical centers) or double bonds; the
racemates, diastereomers, geometric isomers and individual isomers
are encompassed within the scope of the present invention.
[0051] The compounds of the present invention may also contain
unnatural proportions of atomic isotopes at one or more of the
atoms that constitute such compounds. For example, the compounds
may be radiolabeled with radioactive isotopes, such as for example
tritium (.sup.3H), iodine-125 (.sup.125I) or carbon-14 (.sup.14C).
All isotopic variations of the compounds of the present invention,
whether radioactive or not, are intended to be encompassed within
the scope of the present invention.
Description of the Embodiments
I. Inhibitors of Voltage-Dependent Sodium Channels
[0052] In one aspect, the present invention provides compounds
having the formula: ##STR3## or a pharmaceutically acceptable salt
thereof. In Formula I, the symbols R.sup.1 and R.sup.3
independently represent hydrogen, (C.sub.1-C.sub.4)alkyl,
(C.sub.3-C.sub.7)cycloalkyl, (C.sub.1-C.sub.4)haloalkyl,
(C.sub.1-C.sub.6)heteroalkyl, amino, halo, cyano, nitro, hydroxy,
aryl and heteroaryl. R.sup.2 is a moiety selected from hydrogen,
(C.sub.1-C.sub.4)alkyl, (C.sub.1-C.sub.7)cycloalkyl, aryl,
heteroaryl, aryl(C.sub.1-C.sub.4)alkyl, and
heteroaryl(C.sub.1-C.sub.4)alkyl.
[0053] The symbol Y represents a member selected from: ##STR4##
wherein X is selected from O, S and NR.sup.8. The symbol R.sup.8
represents hydrogen, cyano, nitro, alkyl, acyl, aryl or
SO.sub.2R.sup.9. R.sup.9 is selected from alkyl, aryl, heteroaryl
and heterocycloalkyl.
[0054] R.sup.4 and R.sup.5 are independently selected from
hydrogen, (C.sub.1-C.sub.10)alkyl, (C.sub.3-C.sub.7)cycloalkyl,
(C.sub.1-C.sub.8)heteroalkyl, aryl, heteroaryl,
aryl(C.sub.1-C.sub.4)alkyl, heteroaryl(C.sub.1-C.sub.4)alkyl and
(C.sub.3-C.sub.8)heterocycloalkyl, with the proviso that if R.sup.4
is hydrogen, R.sup.5 is not hydrogen. R.sup.4 and R.sup.5 taken
together with the nitrogen atom to which they are attached
optionally form a 4- to 8-membered heterocycloalkyl ring.
[0055] The symbol R.sup.6 represents hydrogen,
(C.sub.1-C.sub.6)alkyl, aryl, heteroaryl,
aryl(C.sub.1-C.sub.4)alkyl, heteroaryl(C.sub.1-C.sub.4)alkyl or
(C.sub.1-C.sub.6)heteroalkyl; and R.sup.7 is selected from
(C.sub.1-C.sub.7)alkyl, (C.sub.3-C.sub.7)cycloalkyl,
(C.sub.1-C.sub.7)alkenyl, (C.sub.1-C.sub.6)heteroalkyl, aryl,
heteroaryl, aryl(C.sub.1-C.sub.4)alkyl,
heteroaryl(C.sub.1-C.sub.4)alkyl, amino, alkoxy,
(C.sub.3-C.sub.8)heterocycloalkyl and amino(C.sub.1-C.sub.5)alkyl.
R.sup.6 and R.sup.7 together with the atoms to which they are
attached optionally form a 4- to 8-membered heterocycloalkyl
ring.
[0056] In a presently preferred embodiment Y is a member selected
from: ##STR5## in which R.sup.4, R.sup.5, R.sup.6, R.sup.7, and X
are as described above.
[0057] In another exemplary embodiment, the invention provides a
compound having a structure according to Formula II: ##STR6## in
which R.sup.1, R.sup.2, R.sup.3, and Y are as described above. In
this embodiment, R.sup.1 and R.sup.3 are preferably each
independently selected from hydrogen, (C.sub.1-C.sub.4)alkyl,
(C.sub.3-C.sub.7)cycloalkyl, (C.sub.1-C.sub.4)haloalkyl and
(C.sub.1-C.sub.5)heteroalkyl. R.sup.2 is preferably selected from
aryl and heteroaryl; and X is preferably O.
[0058] In a further exemplary embodiment, R.sup.4 and R.sup.5 taken
together with the nitrogen to which they are attached form a ring
system such as that set forth below: ##STR7##
[0059] In another preferred embodiment, R.sup.3 is hydrogen;
R.sup.4 is selected from (C.sub.1-C.sub.7)alkyl,
(C.sub.3-C.sub.7)cycloalkyl, aryl, heteroaryl,
aryl(C.sub.1-C.sub.4)alkyl and heteroaryl(C.sub.1-C.sub.4)alkyl;
and R.sup.5 is selected from hydrogen or alkyl. Alternatively,
R.sup.4 and R.sup.5 taken together with the nitrogen atom to which
they are attached form a 4- to 8-membered heterocycloalkyl
ring.
[0060] In yet a further preferred embodiment, the invention
provides a compound in which R.sup.4 is a member selected from:
##STR8## wherein n is an integer from 0 to 4; and k is an integer
from 1 to 3. The symbols R.sup.2a and R.sup.2b are independently
selected from hydrogen and (C.sub.1-C.sub.4)alkyl, and R.sup.2a and
R.sup.2b taken together with the carbon atom to which they are
attached optionally form a 3- to 8-membered carbocyclic or
heterocycloalkyl ring.
[0061] The symbol M represents a moiety that is selected from
NR.sup.10, O and S, wherein R.sup.10 is selected from hydrogen,
(C.sub.1-C.sub.6) alkyl, (C.sub.1-C.sub.8) heteroalkyl aryl,
heteroaryl and (C.sub.3-C.sub.8) cycloalkyl. A, B, D, E and G are
independently moieties selected from N,N-oxide and CR.sup.11, with
the proviso that at most three of A, B, D, E and G is N; and at
most one of A, B, D, E and G is N-oxide.
[0062] R.sup.11 is a member selected from hydrogen, halo, amino,
hydroxy, cyano, nitro, (C.sub.1-C.sub.4)alkyl,
(C.sub.3-C.sub.7)cycloalkyl, (C.sub.1-C.sub.7)heteroalkyl, aryl,
heteroaryl, (C.sub.3-C.sub.8)heterocycloalkyl, alkoxy, acyl,
--C(NR.sup.12)R.sup.13, --SO.sub.2R.sup.15,
--SO.sub.2NR.sup.13R.sup.14, --NR.sup.12SOR.sup.15,
--NR.sup.12SO.sub.2NR.sup.13R.sup.14,
--NR.sup.12C(N--CN)NR.sup.13R.sup.14,
--NR.sup.12C(N--SO.sub.2R.sup.15)NR.sup.13R.sup.14,
--NR.sup.12C(N--COR.sup.15)NR.sup.13R.sup.14,
--CONR.sup.13R.sup.14,
--NR.sup.12(C.dbd.CH--NO.sub.2)NR.sup.13R.sup.14,
--NR.sup.12CONR.sup.13R.sup.14, --NR.sup.12CO--OR.sup.15,
--OCONR.sup.13R.sup.14, and R.sup.11 and R.sup.2a taken together
with the carbon atoms to which they are attached optionally form a
4- to 8-membered heterocycloalkyl group with the proviso that A is
CR.sup.11.
[0063] R.sup.11a is selected from (C.sub.1-C.sub.6)alkyl,
(C.sub.3-C.sub.7)cycloalkyl, (C.sub.3-C.sub.8)heterocycloalkyl,
aryl and heteroaryl. The symbols R.sup.12, R.sup.13 and R.sup.14
independently represent hydrogen, (C.sub.1-C.sub.8)alkyl,
(C.sub.3-C.sub.7)cycloalkyl, (C.sub.1-C.sub.8)heteroalkyl, aryl,
heteroaryl, (C.sub.3-C.sub.8)heterocycloalkyl,
aryl(C.sub.1-C.sub.4)alkyl, heteroaryl(C.sub.1-C.sub.4)alkyl,
amino(C.sub.1-C.sub.4)alkyl and when R.sup.13 and R.sup.14 are
attached to the same nitrogen atom, they are optionally combined to
form a 5-, 6- or 7-membered ring.
[0064] R.sup.15 is selected from (C.sub.1-C.sub.8)alkyl,
(C.sub.3-C.sub.8)cycloalkyl, (C.sub.1-C.sub.8)heteroalkyl, aryl,
heteroaryl and (C.sub.3-C.sub.8)heterocycloalkyl
[0065] When R.sup.4 has a cyclic structure set forth above, R.sup.1
and R.sup.3 are preferably each members independently selected from
hydrogen, (C.sub.1-C.sub.4)alkyl, (C.sub.3-C.sub.7)cycloalkyl,
(C.sub.1-C.sub.4)haloalkyl and (C.sub.1-C.sub.5)heteroalkyl; and X
is O. R.sup.2 is a preferably a member selected from aryl or
heteroaryl.
[0066] In yet another preferred embodiment, the invention provides
a compound in which R.sup.4 has a structure according to Formula
III: ##STR9##
[0067] In Formula III, W is preferably selected from S, SO or
SO.sub.2 or a single bond. SO.sub.2 is presently most preferred.
The symbol R.sup.15 represents a moiety selected from
(C.sub.1-C.sub.4)alkyl, (C.sub.1-C.sub.6)alkenyl,
(C.sub.3-C.sub.7)cycloalkyl, aryl, heteroaryl,
(C.sub.1-C.sub.8)heteroalkyl, NR.sup.16R.sup.17. R.sup.16 and
R.sup.17 are independently selected from hydrogen,
(C.sub.1-C.sub.4)alkyl, (C.sub.1-C.sub.7)cycloalkyl,
(C.sub.1-C.sub.8)heteroalkyl, (C.sub.3-C.sub.8)heterocycloalkyl,
aryl, heteroaryl, aryl(C.sub.1-C.sub.4)alkyl,
heteroaryl(C.sub.1-C.sub.4)alkyl, amino(C.sub.1-C.sub.4)alkyl, with
the proviso that when R.sup.15 is amino W is SO.sub.2;
[0068] The symbols T.sup.1, T.sup.2, T.sup.3 and T.sup.4 are each
independently selected from hydrogen, halo, amino, cyano, nitro,
(C.sub.1-C.sub.4)alkyl, (C.sub.3-C.sub.8)cycloalkyl,
(C.sub.1-C.sub.4)haloalkyl, alkoxy, fluoro(C.sub.1-C.sub.4)alkoxy,
(C.sub.1-C.sub.7)cycloalkyl, (C.sub.1-C.sub.7)heteroalkyl, aryl and
heteroaryl. T.sup.1 and T.sup.2 taken together with the carbon
atoms to which they are attached optionally form a 4- to 8-membered
carbocyclic or heterocycloalkyl ring. T.sup.2 and T.sup.3 taken
together with the carbon atoms to which they are attached
optionally form a 4- to 8-membered carbocyclic or heterocycloalkyl
ring. T.sup.3 and R.sup.15 taken together with the atoms to which
they are attached optionally form a 4- to 8-membered carbocyclic or
heterocycloalkyl ring. T.sup.4 and R.sup.15 taken together with the
atoms to which they are attached optionally form a 4-to 8-membered
carbocyclic or heterocycloalkyl ring.
[0069] In a preferred embodiment, R.sup.1 and R.sup.3 are each
members independently selected from hydrogen,
(C.sub.1-C.sub.4)alkyl, (C.sub.3-C.sub.7)cycloalkyl,
(C.sub.1-C.sub.4)haloalkyl or (C.sub.1-C.sub.5)heteroalkyl; and X
is O. R.sup.2 is preferably a member selected from aryl or
heteroaryl.
[0070] Representative compounds of the invention are set forth in
Example 24 and FIG. 1. Activities towards PN3 of selected compounds
of the invention are provided in Table 1. The compound numbers in
Table 1 are cross-referenced to the compound numbers set forth in
the Example and figures. TABLE-US-00001 TABLE 1 Activity in Flux
Compound # Assay 20 +++ 23 ++ 39 +++ 114 + 154 +++ 323 +++ 411 +++
414 +++ 444 ++ 449 +++ 480 +++ 1054 +++ 1175 ++ (+++ 0.1-4 .mu.M;
++ 4.1-10 .mu.M; + 10.1-30 .mu.M)
[0071] Also within the scope of the present invention are compounds
of the invention that are poly- or multi-valent species, including,
for example, species such as dimers, trimers, tetramers and higher
homologs of the compounds of the invention or reactive analogues
thereof. The poly- and multi-valent species can be assembled from a
single species or more than one species of the invention. For
example, a dimeric construct can be "homodimeric" or
"heterodimeric." Moreover, poly- and multi-valent constructs in
which a compound of the invention or a reactive analogue thereof,
is attached to an oligomeric or polymeric framework (e.g.,
polylysine, dextran, hydroxyethyl starch and the like) are within
the scope of the present invention. The framework is preferably
polyfunctional (i.e. having an array of reactive sites for
attaching compounds of the invention). Moreover, the framework can
be derivatized with a single species of the invention or more than
one species of the invention.
[0072] Moreover, the present invention includes compounds within
the motif set forth in Formula I, which are functionalized to
afford compounds having water-solubility that is enhanced relative
to analogous compounds that are not similarly functionalized. Thus,
any of the substituents set forth herein can be replaced with
analogous radicals that have enhanced water solubility. For
example, it is within the scope of the invention to, for example,
replace a hydroxyl group with a diol, or an amine with a quaternary
amine, hydroxy amine or similar more water-soluble moiety. In a
preferred embodiment, additional water solubility is imparted by
substitution at a site not essential for the ion channel activity
of the compounds set forth herein with a moiety that enhances the
water solubility of the parent compounds. Methods of enhancing the
water-solubility of organic compounds are known in the art. Such
methods include, but are not limited to, functionalizing an organic
nucleus with a permanently charged moiety, e.g., quaternary
ammonium, or a group that is charged at a physiologically relevant
pH, e.g. carboxylic acid, amine. Other methods include, appending
to the organic nucleus hydroxyl- or amine-containing groups, e.g.
alcohols, polyols, polyethers, and the like. Representative
examples include, but are not limited to, polylysine,
polyethyleneimine, poly(ethyleneglycol) and poly(propyleneglycol).
Suitable functionalization chemistries and strategies for these
compounds are known in the art. See, for example, Dunn, R. L., et
al., Eds. POLYMERIC DRUGS AND DRUG DELIVERY SYSTEMS, ACS Symposium
Series Vol. 469, American Chemical Society, Washington, D.C.
1991.
Preparation of Sodium Channel Inhibitors
[0073] Compounds of the present invention may be prepared using
starting materials readily available from commercial suppliers or
known intermediates. Examples of starting materials available from
commercial suppliers include, but are not limited to,
3-methyl-2-phenylpyrazole-4-carboxylic acid,
1-phenyl-5-propyl-1H-pyrazole-4-carboxylic acid,
1-4-chlorophenyl)-5-propyl-1H-pyrazole-4-carboxylic acid,
2-(4-chlorophenyl)-3-trifluoromethyl)pyrazole-4-carboxylic acid,
1-4-(4-chlorophenyl)-1,3-thiazole-2-yl]-5-(trifluoromethyl)-1H-pyrazole-4-
-carboxylic acid,
1-(4-chlorophenyl)-5-methyl-1H-pyrazole-4-carboxylic acid,
5-fluoro-1-phenylpyrazole-4-carboxylic acid and
1-(4-fluorophenyl)-3,5-dimethyl-1H-pyrazole-4-carboxylic acid.
Scheme 1 sets forth an exemplary synthetic scheme for the
preparation of known intermediates used to prepare compounds of the
invention. ##STR10##
[0074] In Scheme 1, anhydride a is contacted with allyl ether b to
form adduct c. The pyrazole ring system d is formed by contacting
adduct c with hydrazine or a hydrazine derivative. The
trifluoromethyl group of the pyrazole ketone d is removed by
treatment with base to afford the carboxylic acid e.
[0075] Numerous routes are available for elaborating the carboxylic
acid moiety of intermediates of the invention. In an exemplary
procedure, the pyrazole carboxylic acid (compound f; Scheme 2) is
activated via conversion to the carboxylic acid chloride (compound
g; Scheme 2) and made to react with an amine (e.g.;
HNR.sup.4R.sup.5) in an organic solvent such as dichloromethane or
tetrahydrofuran in the presence of a base such as triethylamine or
pyridine to give an amide of Formula I where Y is: ##STR11## and X
is O (compound h; Scheme 2). One skilled in the art will recognize
that an amide of the invention may be converted to a thioamido
(i.e.; X is S) by treatment with Lawesson's reagent or other
methods known in the literature. ##STR12##
[0076] Compounds of the present invention may also be prepared as
shown in Schemes 3-6. In Scheme 3, the pyrazole amine (compound i)
is made to react with a carboxylic acid chloride (e.g.;
R.sup.7COCl) using similar conditions described above to give the
amide of formula I where Y is ##STR13## R.sup.6 is H and Z is O.
##STR14##
[0077] In Scheme 4, the pyrazole amine (i) may be made to react
with an isocyanate in an organic solvent such as dichloromethane or
tetrahydrofuran to give the urea (compound k) where Y is ##STR15##
R.sup.6 is H, Z is O and R.sup.7 is amino. Alternatively, the
pyrazole amine (compound i) may be made to react with an
isothiocyanate to give a thiourea (i.e.; Z is S). ##STR16##
[0078] In Scheme 5, the pyrazole amine (i) may be made to react
with the oxazolidinone intermediate (compound l) in an organic
solvent such as tetrahydrofuran, acetonitrile or n-butanol,
typically at elevated temperature (50-100.degree. C.), to give the
sulfenyl urea. Methods used to prepare oxazolidinone are described
in the literature. ##STR17##
[0079] In Scheme 6, the pyrazole amine may be made to react with
the phenoxy intermediate in an organic solvent such as
tetrahydrofuran, acetonitrile or n-butanol, typically at elevated
temperature (50-100.degree. C.), to give the cyanoguanidine.
Methods used to prepare the phenoxy intermediate are described in
the literature. ##STR18## II. Assays for Blockers of Sodium Ion
Channels
[0080] PN3 monomers as well as PN3 alleles and polymorphic variants
are subunits of sodium channels. The activity of a sodium channel
comprising PN3 subunits can be assessed using a variety of in vitro
and in vivo assays, e.g., measuring current, measuring membrane
potential, measuring ion flux, e.g., sodium or guanidinium,
measuring sodium concentration, measuring second messengers and
transcription levels, and using e.g., voltage-sensitive dyes,
radioactive tracers, and patch-clamp electrophysiology.
[0081] A number of experimental models in the rat are appropriate
for assessing the efficacy of the compounds of the invention. For
example, the tight ligation of spinal nerves described by Kim et
al., Pain 50: 355-363 (1992) can be used to experimentally
determine the effect of the compounds of the invention on a PN3
channel. For example, a sodium channel blockade in vitro assay can
be used to determine the effectiveness of compounds of Formula I as
sodium channel blockers in an in vitro model by the inhibition of
compound action potential propagation in isolated nerve
preparations (Kourtney and Stricharz, LOCAL ANESTHETICS,
Springer-Verlag, New York, 1987). The mechanical allodynia in vivo
assay is also of use in determining the efficacy of compounds of
the invention (Kim and Chung Pain 50:355 (1992)). Mechanical
sensitivity can be assessed using a procedure described by Chaplan
et al., J. Neurosci. Methods 53: 55-63 (1994). Other assays of use
are known to those of skill in the art. See, for example, Loughhead
et al., U.S. Pat. No. 6,262,078.
[0082] Inhibitors of the PN3 sodium channels can be tested using
biologically active recombinant PN3, or naturally occurring
TTX-resistant sodium channels, or by using native cells, like cells
from the nervous system expressing a PN3 channel. PN3 channels can
be isolated, co-expressed or expressed in a cell, or expressed in a
membrane derived from a cell. In such assays, PN3 is expressed
alone to form a homomeric sodium channel or is co-expressed with a
second subunit (e.g., another PN3 family member) so as to form a
heteromeric sodium channel. Exemplary expression vectors include,
but are not limited to, PN3-pCDNA3.1. The PN3 channel is stably
expressed in mammalian expression systems.
[0083] Inhibition can be tested using one of the in vitro or in
vivo assays described above. Samples or assays that are treated
with a potential sodium channel inhibitor or activator are compared
to control samples without the test compound, to examine the extent
of inhibition. Control samples (untreated with activators or
inhibitors) are assigned a relative sodium channel activity value
of 100. Inhibition of channels comprising PN3 is achieved when the
sodium channel activity value relative to the control is less than
70%, preferably less than 40% and still more preferably, less than
30%. Compounds that decrease the flux of ions will cause a
detectable decrease in the ion current density by decreasing the
probability of a channel comprising PN3 being open, by decreasing
conductance through the channel, decreasing the number of channels,
or decreasing the expression of channels.
[0084] Changes in ion flux may be assessed by determining changes
in polarization (i.e., electrical potential) of the cell or
membrane expressing the sodium channel. A preferred means to
determine changes in cellular polarization is by measuring changes
in current or voltage with the voltage-clamp and patch-clamp
techniques, using the "cell-attached" mode, the "inside-out" mode,
the "outside-out" mode, the "perforated cell" mode, the "one or two
electrode" mode, or the "whole cell" mode (see, e.g., Ackerman et
al., New Engl. J. Med. 336: 1575-1595 (1997)). Whole cell currents
are conveniently determined using the standard methodology (see,
e.g., Hamil et al., Pflugers. Archiv. 391: 85 (1981). Other known
assays include: radiolabeled rubidium flux assays and fluorescence
assays using voltage-sensitive dyes (see, e.g., Vestergarrd-Bogind
et al., J. Membrane Biol. 88: 67-75 (1988); Daniel et al., J.
Pharmacol. Meth. 25: 185-193 (1991); Holevinsky et al., J. Membrane
Biology 137: 59-70 (1994)). Assays for compounds capable of
inhibiting or increasing sodium flux through the channel proteins
can be performed by application of the compounds to a bath solution
in contact with and comprising cells having a channel of the
present invention (see, e.g., Blatz et al., Nature 323: 718-720
(1986); Park, J. Physiol. 481: 555-570 (1994)). Generally, the
compounds to be tested are present in the range from about 1 pM to
about 100 mM, preferably from about 1 pM to about 1 .mu.M.
[0085] The effects of the test compounds upon the function of the
channels can be measured by changes in the electrical currents or
ionic flux or by the consequences of changes in currents and flux.
Changes in electrical current or ionic flux are measured by either
increases or decreases in flux of ions such as sodium or
guanidinium ions (see, e.g., Berger et al., U.S. Pat. No.
5,688,830). The cations can be measured in a variety of standard
ways. They can be measured directly by concentration changes of the
ions or indirectly by membrane potential or by radio-labeling of
the ions. Consequences of the test compound on ion flux can be
quite varied. Accordingly, any suitable physiological change can be
used to assess the influence of a test compound on the channels of
this invention. The effects of a test compound can be measured by a
toxin-binding assay. When the functional consequences are
determined using intact cells or animals, one can also measure a
variety of effects such as transmitter release, hormone release,
transcriptional changes to both known and uncharacterized genetic
markers, changes in cell metabolism such as cell growth or pH
changes, and changes in intracellular second messengers such as
Ca.sup.2+, or cyclic nucleotides.
[0086] High throughput screening (HTS) is of use in identifying
promising candidates of the invention. Physiologically, Na channels
open and close on a ms timescale. To overcome the short time in
which channels are open the HTS assay can be run in the presence of
an agent that modifies the gating of the channel, such as
deltamethrin. This agent modifies the gating of Na channels and
keeps the pore open for extended periods of time. In addition,
while Na channels are primarily selective for Na, other monovalent
cations can permeate the channel.
[0087] The specificity and effect of the PN3 blocking agents of the
invention can also be assayed against non-specific blockers of PN3,
such as tetracaine, mexilitine, and flecainide.
III. Pharmaceutical Compositions of Sodium Channel Openers
[0088] In another aspect, the present invention provides
pharmaceutical compositions comprising a pharmaceutically
acceptable excipient and a pyrazole, such as a compound according
to Formula I.
Formulation of the Compounds (Compositions)
[0089] The compounds of the present invention can be prepared and
administered in a wide variety of oral, parenteral and topical
dosage forms. Thus, the compounds of the present invention can be
administered by injection, that is, intravenously, intramuscularly,
intracutaneously, subcutaneously, intraduodenally, or
intraperitoneally. Also, the compounds described herein can be
administered by inhalation, for example, intranasally.
Additionally, the compounds of the present invention can be
administered transdermally. Accordingly, the present invention also
provides pharmaceutical compositions comprising a pharmaceutically
acceptable carrier or excipient and a neutral compound of the
invention or a pharmaceutically acceptable salt thereof.
[0090] For preparing pharmaceutical compositions from the compounds
of the present invention, pharmaceutically acceptable carriers can
be either solid or liquid. Solid form preparations include powders,
tablets, pills, capsules, cachets, suppositories, and dispersible
granules. A solid carrier can be one or more substances, which may
also act as diluents, flavoring agents, binders, preservatives,
tablet disintegrating agents, or an encapsulating material.
[0091] In powders, the carrier is a finely divided solid, which is
in a mixture with the finely divided active component. In tablets,
the active component is mixed with the carrier having the necessary
binding properties in suitable proportions and compacted in the
shape and size desired.
[0092] The powders and tablets preferably contain from 5% or 10% to
70% of the active compound. Suitable carriers are magnesium
carbonate, magnesium stearate, talc, sugar, lactose, pectin,
dextrin, starch, gelatin, tragacanth, methylcellulose, sodium
carboxymethylcellulose, a low melting wax, cocoa butter, and the
like. The term "preparation" is intended to include the formulation
of the active compound with encapsulating material as a carrier
providing a capsule in which the active component with or without
other carriers, is surrounded by a carrier, which is thus in
association with it. Similarly, cachets and lozenges are included.
Tablets, powders, capsules, pills, cachets, and lozenges can be
used as solid dosage forms suitable for oral administration.
[0093] For preparing suppositories, a low melting wax, such as a
mixture of fatty acid glycerides or cocoa butter, is first melted
and the active component is dispersed homogeneously therein, as by
stirring. The molten homogeneous mixture is then poured into
convenient sized molds, allowed to cool, and thereby to
solidify.
[0094] Liquid form preparations include solutions, suspensions, and
emulsions, for example, water or water/propylene glycol solutions.
For parenteral injection, liquid preparations can be formulated in
solution in aqueous polyethylene glycol solution.
[0095] Aqueous solutions suitable for oral use can be prepared by
dissolving the active component in water and adding suitable
colorants, flavors, stabilizers, and thickening agents as desired.
Aqueous suspensions suitable for oral use can be made by dispersing
the finely divided active component in water with viscous material,
such as natural or synthetic gums, resins, methylcellulose, sodium
carboxymethylcellulose, and other well-known suspending agents.
[0096] Also included are solid form preparations, which are
intended to be converted, shortly before use, to liquid form
preparations for oral administration. Such liquid forms include
solutions, suspensions, and emulsions. These preparations may
contain, in addition to the active component, colorants, flavors,
stabilizers, buffers, artificial and natural sweeteners,
dispersants, thickeners, solubilizing agents, and the like.
[0097] The pharmaceutical preparation is preferably in unit dosage
form. In such form the preparation is subdivided into unit doses
containing appropriate quantities of the active component. The unit
dosage form can be a packaged preparation, the package containing
discrete quantities of preparation, such as packeted tablets,
capsules, and powders in vials or ampoules. Also, the unit dosage
form can be a capsule, tablet, cachet, or lozenge itself, or it can
be the appropriate number of any of these in packaged form.
[0098] The quantity of active component in a unit dose preparation
may be varied or adjusted from 0.1 mg to 10000 mg, more typically
1.0 mg to 1000 mg, most typically 10 mg to 500 mg, according to the
particular application and the potency of the active component. The
composition can, if desired, also contain other compatible
therapeutic agents.
IV. Methods for Inhibiting Ion Flow in Voltage-Dependent Sodium
Channels
[0099] In yet another aspect, the present invention provides
methods for decreasing ion flow through voltage dependent sodium
channels in a cell, comprising contacting a cell containing the
target ion channels with a sodium channel-inhibiting amount of a
pyrazole, such as a compound of Formula I.
[0100] The methods provided in this aspect of the invention are
useful for the diagnosis of conditions that can be treated by
inhibiting ion flux through voltage-dependent sodium channels, or
for determining if a patient will be responsive to therapeutic
agents, which act by inhibiting sodium channels.
V. Methods for Treating Conditions Mediated by Voltage-Dependent
Sodium Channels
[0101] In still another aspect, the present invention provides a
method for the treatment of a disorder or condition through
inhibition of a voltage-dependent sodium channel. In this method, a
subject in need of such treatment is administered an effective
amount of a pyrazole compound, such as a compound according to
Formula I. In a preferred embodiment, the compounds provided herein
are used to treat a disorder or condition by inhibiting an ion
channel of the voltage gated sodium channel family, e.g., PN3.
[0102] The compounds provided herein are useful as sodium channel
inhibitors and find therapeutic utility via inhibition of
voltage-dependent sodium channels in the treatment of diseases or
conditions. The sodium channels that are typically inhibited are
described herein as voltage-dependent sodium channels such as the
PN3 sodium channels.
[0103] The compounds of the invention are particularly preferred
for use in the treating, preventing or ameliorating pain or
seizures. The method includes administering to a patient in need of
such treatment, a therapeutically effective amount of a pyrazole
compound, e.g., a compound of the invention or a pharmaceutically
acceptable salt thereof.
[0104] The compounds, compositions and methods of the present
invention are of particular use in treating pain, including both
inflammatory and neuropathic pain. Exemplary forms of pain treated
by a compound of the invention include, postoperative pain,
osteoarthritis pain, pain associated with metastatic cancer,
neuropathy secondary to metastatic inflammation, trigeminal
neuralgia, glossopharangyl neuralgia, adiposis dolorosa, burn pain,
acute herpetic and postherpetic neuralgia, diabetic neuropathy,
causalgia, brachial plexus avulsion, occipital neuralgia, reflex
sympathetic dystrophy, fibromyalgia, gout, phantom limb pain, burn
pain, pain following stroke, thalamic lesions, radiculopathy, and
other forms of neuralgic, neuropathic, and idiopathic pain
syndromes.
[0105] Idiopathic pain is pain of unknown origin, for example,
phantom limb pain. Neuropathic pain is generally caused by injury
or infection of the peripheral sensory nerves. It includes, but is
not limited to pain from peripheral nerve trauma, herpes virus
infection, diabetes mellitus, causalgia, plexus avulsion, neuroma,
limb amputation, and vasculitis. Neuropathic pain is also caused by
nerve damage from chronic alcoholism, human immunodeficiency virus
infection, hypothyroidism, uremia, or vitamin deficiencies.
[0106] Moreover, any sodium channel inhbitory substance possessed
of satisfactory sodium channel inhibiting activity coupled with
favorable intracranial transfer kinetics and metabolic stability is
expected to show good efficacy in central nervous system (CNS)
diseases and disorders such as central nervous system ischemia,
central nervous system trauma (e.g. brain trauma, spinal cord
injury, whiplash injury, etc.), epilepsy, seizures,
neurodegenerative diseases (e.g. amyotrophic lateral sclerosis
(ALS), Alzheimer's disease, Huntington's chorea, Parkinson's
disease, diabetic neuropathy, etc.), vascular dementia (e.g.
multi-infarct dementia, Binswanger's disease, etc.),
manic-depressive psychosis, depression, schizophrenia, chronic
pain, trigeminal neuralgia, migraine, ataxia, bipolar disorder,
spasticity, mood disorders, psychotic disorders, hearing and vision
loss, age-related memory loss, learning deficiencies, anxiety and
cerebral edema.
[0107] In treatment of the above conditions, the compounds utilized
in the method of the invention are administered at the initial
dosage of about 0.001 mg/kg to about 1000 mg/kg daily. A daily dose
range of about 0.1 mg/kg to about 100 mg/kg is more typical. The
dosages, however, may be varied depending upon the requirements of
the patient, the severity of the condition being treated, and the
compound being employed. Determination of the proper dosage for a
particular situation is within the skill of the practitioner.
Generally, treatment is initiated with smaller dosages, which are
less than the optimum dose of the compound. Thereafter, the dosage
is increased by small increments until the optimum effect under the
circumstances is reached. For convenience, the total daily dosage
may be divided and administered in portions during the day, if
desired.
EXAMPLES
[0108] The following examples are offered to illustrate, but not to
limit the claimed invention.
[0109] In the examples below, unless otherwise stated, temperatures
are given in degrees Celsius (.degree. C.); operations were carried
out at room or ambient temperature (typically a range of from about
18-25.degree. C.; evaporation of solvent was carried out using a
rotary evaporator under reduced pressure (typically, 4.5-30 mmHg)
with a bath temperature of up to 60.degree. C.; the course of
reactions was typically followed by thin layer chromatography and
reaction times are provided for illustration only; products
exhibited satisfactory .sup.1H-NMR and/or LCMS data; yields (when
provided) are for illustration only; and the following conventional
abbreviations are also used: mp (melting point), L (liter), mL
(milliliters), mmol (millimoles), g (grams), mg (milligrams), min
(minutes), LCMS (liquid chromatography-mass spectrometry) and h
(hours), PS (polystyrene), DIEA (diisopropylethylamine).
Example 1
Preparation of
1-(3-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-carboxylic
acid
[0110] ##STR19##
[0111] 1,1,1,5,5,5-Hexafluoro-3-isobutoxymethylen-pentane-2,4-dione
was prepared according to experimental procedures described in
Synthesis 1990, 347-350.
[0112] 3-Chlorophenylhydrazine (1.04 g, 7.29 mmol) was added to a
solution of
1,1,1,5,5,5-hexafluoro-3-isobutoxymethylen-pentane-2,4-dione (2.13
g, 7.29 mmol) in acetonitrile (3 mL) at 0.degree. C. The reaction
mixture was warmed to room temperature, stirred for 16 h and
concentrated under reduced pressure. The crude residue was treated
with methanol (25 mL) and potassium hydroxide (2.00 g) and the
reaction mixture refluxed for 18 h. The reaction mixture was
concentrated under reduced pressure and the crude product was taken
up in water, acidified with 6M hydrochloric acid and extracted with
ethyl acetate (5.times.50 mL). The organic layers were collected,
concentrated and crude product purified by column chromatography on
silica gel to give
1-(3-chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-carboxylic
acid. LCMS m/z=288.9(M-H).sup.-.
Example 2
Preparation of
1-(4-chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-carboxylic
acid-pyridine-4-ylamide
[0113] ##STR20##
[0114] 1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-carbonyl
chloride (0.100 g, 0.324 mmol) was added to a solution of
4-aminopyridine (0.036 g, 0.387 mmol) and pyridine (0.078 mL, 0.969
mmol) in acetonitrile (10 mL). The reaction mixture was heated at
60.degree. C. for 12 h, concentrated and the crude product was
purified by column chromatography on silica gel to give
1-(4-chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid
pyridine-4-ylamide. LCMS m/z=366.9 (M+H).sup.+.
Example 3
Preparation of
1-(4-chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid
(3-methane sulfonyl-phenyl)-amide
[0115] ##STR21##
[0116] 1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-carbonyl
chloride (0.250 g, 0.808 mmol) was added to a solution of
3-methylsulfonylaniline hydrochloride (0.184 g, 0.889 mmol) and
triethylamine (0.563 mL, 4.04 mmol) in acetonitrile (20 mL). The
reaction mixture heated at 60.degree. C. for 12 h, concentrated and
crude product purified by column chromatography on silica gel to
give 1-(4-chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-carboxylic
acid (3-methane sulfonyl-phenyl)-amide. .sup.1H-NMR (CD.sub.3OD,
300 MHz) .delta. 8.37 (s, 1H), 8.17 (s, 1H), 7.97 (d, 1H, J=8.5
Hz), 7.73 (d, 1H, J=8.0 Hz), 7.59-7.66 (m, 3H), 7.51 (d, 2H, J=8.8
Hz), 3.15 (s, 3H); LCMS m/z=443.9 (M+H).sup.+.
Example 4
Preparation of
1-(4-chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid
[2-(3-fluoro-phenyl)-ethyl]-amide
[0117] ##STR22##
[0118] 1-(4-chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-carbonyl
chloride (0.100 g, 0.324 mmol) was added to a solution of
2-(3-fluoro-phenyl)ethylamine (0.051 mL, 0.389 mmol) and
triethylamine (0.135 mL, 0.972 mmol) in acetonitrile (10 mL). The
reaction mixture stirred for 1 hr at room temperature, concentrated
and crude product purified by column chromatography on silica gel
to give
1-(4-chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid
[2-(3-fluoro-phenyl)-ethyl]-amide. LCMS m/z=412.0 (M+H).sup.+.
Example 5
Preparation of
1-(3-chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid
3-trifluoromethyl-benzylamide)
[0119] ##STR23##
[0120] Benzotriazole-1-yloxytris(dimethylamino)phosphonium
hexafluorophosphate (BOP) (0.083 g; 0.189 mmol) was added to a
solution of
1-(3-chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid
(0.050 g; 0.172 mmol), 3-trifluoromethyl benzylamine (0.030 g;
0.206 mmol) and triethylamine (0.072 mL; 0.516 mmol) in
tetrahydrofuran (10 mL). The reaction mixture was stirred at room
temperature for 4 h, concentrated and the crude product purified by
column chromatography on silica gel to give
1-(3-chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid
3-trifluoromethyl-benzylamide. LCMS m/z=448.8 (M+H).sup.+.
Example 6
Preparation of
1-(4-chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid
(2,4-difluoro-phenyl)-amide)
[0121] ##STR24##
[0122] 2-4-difluoro-phenylamine (0.004 g; 0.029 mmL) was added to a
suspension of
1-(4-chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-carbonyl
chloride (0.010 g; 0.032 mmol) and PS-DIEA (0.1 g) in acetonitrile
(2 mL). The reaction mixture was shaken at room temperature for 12
h at which time PS-trisamine (0.1 g) was added to remove the excess
acid chloride. After an additional 12 h of shaking, the reaction
mixture was filtered and concentrated to give
1-(4-chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid
(2,4-difluoro-phenyl)-amide. LCMS m/z=399.8 (M-H).sup.-.
Example 7
Preparation of
1-(4-chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid
(2-fluoro-3-trifluoromethyl-phenyl)-amide
[0123] ##STR25##
[0124] 2-Fluoro-3-trifluoromethyl-phenylamine (0.007 g; 0.039 mmol)
was added to a suspension of
1-(4-chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-carbonyl
chloride (0.010 g; 0.032 mmol) and PS-DIEA (0.1 g) in acetonitrile
(2 mL). The reaction mixture was shaken at room temperature for 12
h at which time PS-TSCl (0.2 g) high loading was added to remove
the excess amine. After an additional 12 h of shaking, the reaction
mixture was filtered and concentrated to give
1-(4-chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid
(2-fluoro-3-trifluoromethyl-phenyl)-amide. LCMS m/z=449.9
(M-H).sup.-.
Example 8
Preparation of
1-(4-fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid
3-trifluoromethyl-benzylamide
[0125] ##STR26##
[0126] 3-Trifluoromethyl benzylamine (0.014 mL, 0.100 mmole) was
added to a suspension of
1-(4-fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid
(0.030 g; 0.109 mmol) and PS-Carbodiimide (0.2 g) in methylene
chloride (2 mL). The reaction mixture was shaken at room
temperature for 12 h at which time the reaction mixture was
filtered and concentrated to give
1-(4-fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid
3-trifluoromethyl-benzylamide. LCMS m/z=432.3 (M+H).sup.+.
Example 9
Preparation of
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4-ylamine
[0127] ##STR27##
[0128] Bromine (4.70 mL, 100 mmol) was added to a solution of
1-(4-chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid
amide (1.20 g, 4.15 mmol) in 3M NaOH (100 mL). The reaction mixture
was heated at 100.degree. C. for 1 hour, cooled to room temperature
and extracted with EtOAc (3.times.50 mL). Organic layers were
collected, concentrated and crude product purified by column
chromatography to give
1-(4-chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4-ylamine (0.408
g, 38%).
Example 10
Preparation of
1-[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4-yl]-3-(3-methanesul-
fonyl-phenyl)-urea
[0129] ##STR28##
[0130] Triphosgene (0.042 g, 0.140 mmol) was added to a solution of
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4-ylamine (0.100
g, 0.382 mmol) and Na.sub.2CO.sub.3 (0.405 g, 3.82 mmol) in
CH.sub.2Cl.sub.2/H.sub.2O (50 mL, 1:1) and stirred at room
temperature for 30 min. 3-Methanesulfonyl-phenylamine HCl (0.095 g,
0.458 mmol) was added to the reaction mixture, stirred at room
temperature for 2 hrs, organic layer collected and aqueous layer
extracted with EtOAc (3.times.25 mL). Organic layers were
collected, concentrated and crude product purified by column
chromatography to give
1-[1-(4-chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4-yl]-3-(3-methanesul-
fonyl-phenyl)-urea (0.040 g, 22%).
Example 11
[0131] ##STR29##
[0132] Excess 3,4-dichlorophenylisocyanate was added to a solution
of 1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4-ylamine (13.1
mg, 0.05 mmol) in THF (1 mL). The reaction was shaken overnight
then the excess 3,4-dichlorophenylisocyanate was scavenged with
PS-trisamine. The product (21.4 mg, 95%) was isolated by filtration
and evaporation.
Example 12
Preparation of
3-{[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-carbonyl]-amino}--
benzenesulfonyl fluoride
[0133] ##STR30##
[0134] 1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-carbonyl
chloride (3.00 g, 9.70 mmol) was added to 3-amino-benzenesulfonyl
fluoride (1.87 g, 10.6 mmol) in CH.sub.2Cl.sub.2 (50 ml) containing
pyridine (2.35 ml, 29.1 mmol). Reaction mixture stirred overnight
at room temperature, concentrated under reduced pressure and crude
product purified by column chromatography to give
3-{[1-(4-chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-carbonyl]-amino}--
benzenesulfonyl fluoride (3.23 g, 74%).
Example 13
Preparation of
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid
(3-cyclopropylsulfamoyl-phenyl)-amide
[0135] ##STR31##
[0136] Cyclopropyl amine (0.012 mL, 0.167 mmol) was added to
3-{[1-(4-chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-carbonyl]-amino}--
benzenesulfonyl fluoride (0.025 g, 0.055 mmol) in CH.sub.2Cl.sub.2
(10 ml). Reaction mixture stirred overnight at room temperature,
concentrated under reduced pressure and crude product purified by
column chromatography to give
1-(4-chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid
(3-cyclopropylsulfamoyl-phenyl)-amide (0.015 g, 55%).
Example 14
Preparation of
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid
(3-cyano-2-phenyl-isourea)-amide
[0137] ##STR32##
[0138] Diphenyl N-cyanocarbonimidate (0.235 g, 0.984 mmol) was
added to
1-(4-chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid
(3-amino-phenyl)-amide (0.250 g, 0.656 mmol) in CH.sub.3CN (10 mL)
and heated at 80.degree. C. overnight. Reaction mixture
concentrated under reduced pressure and crude product purified by
column chromatography to give
1-(4-chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid
(3-cyano-2-phenyl-isourea)-amide (0.258 g, 75%).
Example 15
Preparation of
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid
N'-methyl-cyanoguanidine
[0139] ##STR33##
[0140]
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid
(3-cyano-2-phenyl-isourea)-amide (0.050 g, 0.095 mmol) was added to
a solution of methyl amine (10 mL, 20 mmol, 2M in THF) and stirred
overnight. Reaction mixture concentrated under reduced pressure and
crude product purified by column chromatography to give
1-(4-chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid
N'-methyl-cyanoguanidine (0.038 g, 88%).
Example 16
Preparation of
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid
(3-methylsulfone-2-phenyl-isourea)-amide
[0141] ##STR34##
[0142] Diphenyl N-methylsulfone-carbonimidate (0.573 g, 1.97 mmol)
was added to
1-(4-chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid
(3-amino-phenyl)-amide (0.500 g, 1.31 mmol) in CH.sub.3CN (20 mL)
and heated at 80.degree. C. for 2 days. Reaction mixture
concentrated under reduced pressure and crude product purified by
column chromatography to give
1-(4-chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid
(3-methylsulfone-2-phenyl-isourea)-amide (0.700 g, 92%).
Example 17
Preparation of
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid
[3-(N'-methylsulfone-N''-cyclopropyl-guanidino)-phenyl]-amide
[0143] ##STR35##
[0144]
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid
(3-methylsulfone-2-phenyl-isourea)-amide (0.025 g, 0.0432 mmol) was
added to a solution of cyclopropyl amine (0.030 mL, 0.432 mmol) in
THF (5 mL) and stirred overnight. Reaction mixture concentrated
under reduced pressure and crude product purified by column
chromatography to give
1-(4-chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid
[3-(N'-methylsulfone-N''-cyclopropyl-guanidino)-phenyl]-amide
(0.015 g, 65%).
Example 18
Preparation of
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid
(3-boronic acid-phenyl)-amide
[0145] ##STR36##
[0146] 1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-carbonyl
chloride (0.100 g, 0.323 mmol) was added to 3-amino-boronic acid
monohydrate (0.060 g, 0.388 mmol) in CH.sub.2Cl.sub.2 (5 ml)
containing pyridine (0.078 ml, 0.970 mmol). Reaction mixture
stirred 2 hours at 80.degree. C., concentrated under reduced
pressure and crude product purified by column chromatography to
give 1-(4-chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-carboxylic
acid (3-boronic acid-phenyl)-amide. (0.130 g, 98%).
Example 19
Preparation of
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid
(3-thiazol-2-yl-phenyl)-amide
[0147] ##STR37##
[0148] Dichlorobis(triphenylphosphine)palladium (II) (0.002 g,
0.00244 mmol) was added to a degassed (N.sub.2) mixture of
1-(4-chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid
(3-boronic acid-phenyl)-amide (0.100 g, 0.244 mmol),
Na.sub.2CO.sub.3 (0.052 g, 0.488 mmol), and 2-Bromo-thiazole (0.048
g, 0.292 mmol) in H.sub.2O/toluene (1 mL/2 mL). Reaction mixture
heated at 80.degree. C. for 12 hours, cooled to room temperature
and extracted with EtOAc (3.times.5 mL). Organic layers were
collected, concentrated and crude product purified by column
chromatography to give
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid
(3-thiazol-2-yl-phenyl)-amide (0.074 g, 67%).
Example 20
Preparation of
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid
(3-sulfamide-phenyl)-amide
[0149] ##STR38##
[0150] Sulfamide (0.010 g, 0.105 mmol) was added to
1-(4-chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid
(3-amino-phenyl)-amide (0.020 g, 0.00525 mmol) in 1,4-dioxane (2
mL) and heated at 120.degree. C. overnight. Reaction mixture
concentrated under reduced pressure and crude product purified by
column chromatography to give
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid
(3-sulfamide-phenyl)-amide (0.013 g, 54%).
Example 21
Preparation of
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid
(3-dimethylsulfamide-phenyl)-amide
[0151] ##STR39##
[0152] Dimethylsulfamoyl chloride (0.010 g, 0.105 mmol) was added
to 1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-carboxylic
acid (3-amino-phenyl)-amide (0.025 g, 0.0656 mmol) in CH.sub.3CN (2
mL) containing pyridine (0.016 mL, 0.196 mmol). Reaction mixture
stirred overnight, concentrated under reduced pressure and crude
product purified by column chromatography to give
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid
(3-dimethylsulfamide-phenyl)-amide (0.019 g, 59%).
Example 22
.sup.14C Guanidinium Ion Influx Binding Assay
[0153] PN3 stably expressed in a host cell line were maintained in
DMEM with 5% fetal bovine serum and 300 .mu.g/ml G-418. The cells
were subcultured and grown to confluence in 96-well plates 24-48 h
before each experiment. After the growth medium was removed, the
cells were washed with warm buffer (25 mM Hepes-Tris, 135 mM
choline chloride, 5.4 mM potassium chloride, 0.98 mM magnesium
sulfate, 5.5 mM glucose, and 1 mg/ml BSA, pH 7.4) and incubated in
buffer on a 36.degree. C. slide warmer for approximately 10
minutes. Various concentrations of the test compounds or standard
sodium channel blockers (10 .mu.M) and then deltamethrine (10
.mu.M) were added to each well. After the cells were exposed to
deltamethrine for 5 minutes, 5 .mu.M of .sup.14C-guanidinium was
added, incubated with the radioligand (30-60 min), washed with
ice-cold buffer, and dissolved in 0.1N sodium hydroxide. The
radioactivity and the protein concentration of each cell lysate
were determined by liquid scintillation counting and the protein
assay using Pierce BCA reagent.
Example 23
23.1 Mechanical Allodynia In vivo Assay
[0154] This assay determines the effectiveness of compounds of
Formula I in relieving one of the symptoms in an in vivo model of
neuropathic pain produced by spinal nerve ligation, namely
mechanical allodynia.
[0155] Tactile allodynia was induced in rats using the procedures
described by Kim and Chung, Pain 50: 355-363 (1992). Briefly, the
rats were anesthetized with 2-5% inhaled isoflurane and maintained
by 1% isoflurane. Each animal was then placed in a prone position,
a 3 cm lateral incision was made, and the left paraspinal muscles
separated from the spinous process at the L.sub.4-S.sub.2 level.
The L.sub.6 transverse process was then removed in order to
visually identify the L.sub.4-L.sub.6 spinal nerves. The L.sub.5
and L.sub.6 spinal nerves were then individually isolated and
tightly ligated with silk thread. The wound was then closed in
layers by silk sutures. These procedures produced rats which
developed a significant increase in sensitivity to mechanical
stimuli that did not elicit a response in normal rats.
[0156] Mechanical sensitivity was assessed using a procedure
described by Chaplan et al., J. Neurosci. Methods 53: 55-63 (1994).
Briefly, a series of eight Von Frey filaments of varying rigidity
strength were applied to the plantar surface of the hind paw
ipsilaterial to the ligations with just enough force to bend the
filament. The filaments were held in this position for no more than
three seconds or until a positive allodynic response was displayed
by the rat. A positive allodynic response consisted of lifting the
affected paw followed immediately by licking or shaking of the paw.
The order and frequency with which the individual filaments were
applied were determined by using Dixon up-down method. Testing was
initiated with the middle hair of the series with subsequent
filaments being applied in consecutive fashion, either ascending or
descending, depending on whether a negative or positive response,
respectively, was obtained with the initial filament.
23.2 Thermal Hyperalgesia In vivo Assay
[0157] This assay determines the effectiveness of compounds in
relieving one of the symptoms of neuropathic pain produced by
unilateral mononeuropathy, namely thermal hyperalgesia.
[0158] The rats having had surgery as described above were assessed
for thermal hyperalgesia sensitivity at least 5-7 days
post-surgery. Briefly, the rats were placed beneath inverted
plexiglass cages upon an elevated glass platform and a radiant heat
source beneath the glass was aimed at the plantar hindpaw. The
duration of time before the hindpaw was withdrawn from the floor
was measured to the nearest tenth of a second. The cutoff time for
the heat stimulus was 40 seconds, and the light was calibrated such
that this stimulus duration did not burn or blister the skin. Three
latency measurements were taken for each hindpaw ipsilateral to the
ligation in each test session, alternating left and right hindpaws,
with greater than 1 minute intervals between tests.
23.3 Results
[0159] The results show that after oral administration the
compounds of the invention produce efficacious anti-allodynic
effects at doses less then or equal to 100 mg/kg. The results show
that after IV administration the compounds of the invention produce
efficacious anti-hyperalgesic effects at doses less than or equal
to 30 mg/kg. Overall, the compounds of the present invention were
found to be effective in reversing mechanical allodynia-like and
thermal hyperalgesia-like symptoms.
Example 24
[0160] Example 24 sets forth representative compounds of the
invention. TABLE-US-00002 compound # name MZ 1
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 423 carboxylic
acid (benzo[1,3]dioxol-5-ylmethyl)-amide 2
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 380 carboxylic
acid (pyridin-2-ylmethyl)-amide 3
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 380 carboxylic
acid (pyridin-3-ylmethyl)-amide 4
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 380 carboxylic
acid (pyridin-4-ylmethyl)-amide 5
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 467 carboxylic
acid (2,4,6-trichloro-phenyl)-amide 6
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 447 carboxylic
acid 3,4-dichloro-benzylamide 7
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 429 carboxylic
acid [3-(4-methyl-piperazin-1-yl)-propyl]-amide 8
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 461 carboxylic
acid [2-(2,4-dichloro-phenyl)-ethyl]-amide 9
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 467 carboxylic
acid [2-(3,4-dimethoxy-phenyl)-ethyl]-methyl-amide 10
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 455 carboxylic
acid (biphenyl-3-ylmethyl)-amide 11
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 370 carboxylic
acid (5-methyl-isoxazol-3-yl)-amide 12
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 355 carboxylic
acid (1H-pyrazol-3-yl)-amide 13
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 380 carboxylic
acid (4-cyano-2H-pyrazol-3-yl)-amide 14
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 383 carboxylic
acid (2-ethyl-2H-pyrazol-3-yl)-amide 15
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 371 carboxylic
acid (5-hydroxy-1H-pyrazol-3-yl)-amide 16
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 356 carboxylic
acid isoxazol-3-ylamide 17
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 431 carboxylic
acid (5-phenyl-2H-pyrazol-3-yl)-amide 18
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 383 carboxylic
acid (2,5-dimethyl-2H-pyrazol-3-yl)-amide 19
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 448 carboxylic
acid (4-bromo-5-methyl-isoxazol-3-yl)-amide 20
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 445 carboxylic
acid (2-methyl-5-phenyl-2H-pyrazol-3-yl)-amide 21
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 447 carboxylic
acid (5-oxo-1-phenyl-4,5-dihydro-1H-pyrazol- 3-yl)-amide 22
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 366 carboxylic
acid pyridin-3-ylamide 23
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 366 carboxylic
acid pyridin-4-ylamide 24
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 447 carboxylic
acid 3-trifluoromethyl-benzylamide 25
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 447 carboxylic
acid 4-trifluoromethyl-benzylamide 26
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 508 carboxylic
acid [2-(3-chloro-4-fluoro-phenyl)-4-cyano- 2H-pyrazol-3-yl]-amide
27 1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 458
carboxylic acid (5-bromo-6-methyl-pyridin-2-yl)-amide 28
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 453 carboxylic
acid [2-(3,5-dimethoxy-phenyl)-ethyl]-amide 29
1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic acid [2-(3,5- 393
dimethoxy-phenyl)-ethyl]-amide 30
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 439 carboxylic
acid 2,6-dimethoxy-benzylamide 31
1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic acid 2,6- 379
dimethoxy-benzylamide 32
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 432 carboxylic
acid [2-(1H-indol-3-yl)-ethyl]-amide 33
1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic acid [2-(1H- 372
indol-3-yl)-ethyl]-amide 34
2-{[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole- 375
4-carbonyl]-amino}-propionic acid methyl ester 35
2-[(1-Phenyl-5-propyl-1H-pyrazole-4-carbonyl)-amino]- 315 propionic
acid methyl ester 36
2-{[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole- 417
4-carbonyl]-amino}-propionic acid methyl ester 37
4-Methyl-2-[(1-phenyl-5-propyl-1H-pyrazole-4-carbonyl)- 357
amino]-pentanoic acid methyl ester 38
2-{[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole- 451
4-carbonyl]-amino}-3-phenyl-propionic acid methyl ester 39
3-Phenyl-2-[(1-phenyl-5-propyl-1H-pyrazole-4-carbonyl)- 391
amino]-propionic acid methyl ester 40
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 451 carboxylic
acid (3-fluoro-5-trifluoromethyl-phenyl)-amide 41
1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic acid (3- 391
fluoro-5-trifluoromethyl-phenyl)-amide 42
2-{[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole- 490
4-carbonyl]-amino}-3-(1H-indol-3-yl)-propionic acid methyl ester 43
3-(1H-Indol-3-yl)-2-[(1-phenyl-5-propyl-1H-pyrazole-4- 430
carbonyl)-amino]-propionic acid methyl ester 44
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 453 carboxylic
acid [2-(3,4-dimethoxy-phenyl)-ethyl]-amide 45
1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic acid [2-(3,4- 393
dimethoxy-phenyl)-ethyl]-amide 46
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 399 carboxylic
acid (2-thiophen-2-yl-ethyl)-amide 47
1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic acid (2- 339
thiophen-2-yl-ethyl)-amide 48
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 369 carboxylic
acid (furan-2-ylmethyl)-amide 49
1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic acid (furan- 309
2-ylmethyl)-amide 50
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 394 carboxylic
acid (2-pyridin-2-yl-ethyl)-amide 51
1-Phenyl-5-propyl-1H-pyazole-4-carboxylic acid (2- 334
pyridin-2-yl-ethyl)-amide 52
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 448 carboxylic
acid (1-benzyl-pyrrolidin-3-yl)-amide 53
1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic acid (1- 388
benzyl-pyrrolidin-3-yl)-amide 54
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 385 carboxylic
acid (thiophen-2-ylmethyl)-amide 55
1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic acid 325
(thiophen-2-ylmethyl)-amide 56
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 419 carboxylic
acid (1H-benzoimidazol-2-ylmethyl)-amide 57
1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic acid (1H- 359
benzoimidazol-2-ylmethyl)amide 58
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 400 carboxylic
acid (1-ethyl-pyrrolidin-2-ylmethyl)-amide 59
1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic acid (1- 340
ethyl-pyrrolidin-2-ylmethyl)-amide 60
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 394 carboxylic
acid (2-pyridin-3-yl-ethyl)-amide 61
1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic acid (2- 334
pyridin-3-yl-ethyl)-amide 62
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 409 carboxylic
acid (2-phenoxy-ethyl)-amide 63
1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic acid (2- 349
phenoxy-ethyl)-amide 64
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 414 carboxylic
acid [3-(2-oxo-pyrrolidin-1-yl)-propyl]-amide 65
1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic acid [3-(2- 354
oxo-pyrrolidin-1-yl)-propyl]-amide 66
1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic acid 395
(biphenyl-3-ylmethyl)-amide 67
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 515 carboxylic
acid 3,5-bis-trifluoromethyl-benzylamide 68
1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic acid 3,5-bis- 455
trifluoromethyl-benzylamide 69
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 424 carboxylic
acid 4-nitro-benzylamide 70
1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic acid 4-nitro- 364
benzylamide 71 1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
397 carboxylic acid (3-imidazol-1-yl-propyl)-amide 72
1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic acid (3-imidazol- 337
1-yl-propyl)-amide 73
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 373 carboxylic
acid (tetrahydro-furan-2-ylmethyl)-amide 74
1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic acid 313
(tetrahydro-furan-2-ylmethyl)-amide 75
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 385 carboxylic
acid cyclohexylmethyl-amide 76
1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic acid 325
cyclohexylmethyl-amide 77
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 345 carboxylic
acid isobutyl-amide 78 1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic
acid 285 isobutyl-amide 79
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 405 carboxylic
acid indan-1-ylamide 80 1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic
acid indan- 345 1-ylamide 81
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 357 carboxylic
acid cyclopentylamide 82 1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic
acid 297 cyclopentylamide 83
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 402 carboxylic
acid (2-morpholin-4-yl-ethyl)-amide 84
1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic acid (2-morpholin- 342
4-yl-ethyl)-amide 85
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 439 carboxylic
acid 3,5-dimethoxy-benzylamide 86
1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic acid 3,5- 379
dimethoxy-benzylamide 87 1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic
acid 363 (benzo[1,3]dioxol-5-ylmethyl)-amide 88
1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic acid 3- 387
trifluoromethyl-benzylamide 89
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 360 carboxylic
acid (2-dimethylamino-ethyl)-amide 90
1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic acid (2- 300
dimethylamino-ethyl)-amide 91
{[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 389
carbonyl]-methyl-amino}-acetic acid ethyl ester 92
[Methyl-(1-phenyl-5-propyl-1H-pyrazole-4-carbonyl)- 329
amino]-acetic acid ethyl ester 93
[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4-yl]- 343
pyrrolidin-1-yl-methanone 94
(1-Phenyl-5-propyl-1H-pyrazol-4-yl)-pyrrolidin-1-yl- 283 methanone
95 [1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4-yl]- 405
(3,4-dihydro-1H-isoquinolin-2-yl)-methanone 96
(3,4-Dihydro-1H-isoquinolin-2-yl)-(1-phenyl-5-propyl- 345
1H-pyrazol-4-yl)-methanone 97
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 407 carboxylic
acid benzyl-ethyl-amide 98
1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic acid benzyl- 347
ethyl-amide 99
[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4-yl]- 375
thiomorpholin-4-yl-methanone 100
(1-Phenyl-5-propyl-1H-pyrazol-4-yl)-thiomorpholin-4-yl- 315
methanone 101
1-[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 414
carbonyl]-pyrrolidine-2-carboxylic acid dimethylamide 102
1-(1-Phenyl-5-propyl-1H-pyrazole-4-carbonyl)-pyrrolidine- 354
2-carboxylic acid dimethylamide 103
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 514 carboxylic
acid (2-methoxy-benzyl)-(2-pyridin-2-yl- ethyl)-amide 104
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 552 carboxylic
acid (3,4-dichloro-benzyl)-(2-pyridin-2-yl- ethyl)-amide 105
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 502 carboxylic
acid (4-fluoro-benzyl)-(2-pyridin-2-yl-ethyl)-amide 106
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 498 carboxylic
acid (4-methyl-benzyl)-(2-pyridin-2-yl-ethyl)- amide 107
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 552 carboxylic
acid (3,4-dichloro-benzyl)-(2-pyridin-3-yl- ethyl)-amide 108
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 543 carboxylic
acid (3,4-dimethoxy-benzyl)-(1-phenyl-ethyl)- amide 109
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 446 carboxylic
acid (2-cyano-ethyl)-phenethyl-amide 110
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 552 carboxylic
acid (3,4-dichloro-benzyl)-(2-pyridin-4-yl- ethyl)-amide 111
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 440 carboxylic
acid (5-chloro-benzooxazol-2-yl)-amide 112
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 434 carboxylic
acid (3,5-dichloro-pyridin-2-yl)-amide 113
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 400 carboxylic
acid (5-chloro-pyridin-2-yl)-amide 114
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 393 carboxylic
acid phenethyl-amide 115
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 394 carboxylic
acid (2-pyridin-4-yl-ethyl)-amide 116
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 468 carboxylic
acid (3-chloro-5-trifluoromethyl-pyridin-2-yl)- amide 117
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 464 carboxylic
acid (3-diethylcarbamoyl-phenyl)-amide
118 1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 525
carboxylic acid [4-(5-methyl-isoxazol-3-ylsulfamoyl)-phenyl]- amide
119 1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 399
carboxylic acid (2-chloro-phenyl)-amide 120
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 447 carboxylic
acid (1-ethyl-2-methyl-1H-benzoimidazol-5- yl)-amide 121
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 512 carboxylic
acid [4-(6-methyl-benzothiazol-2-yl)phenyl]-amide 122
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 471 carboxylic
acid (2-methoxy-biphenyl-4-yl)-amide 123
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 405 carboxylic
acid (1H-indazol-6-yl)-amide 124
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 365 carboxylic
acid phenylamide 125 1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic
acid (3- 404 diethylcarbamoyl-phenyl)-amide 126
1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic acid [4-(5- 465
methyl-isoxazol-3-ylsulfamoyl)-phenyl]-amide 127
1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic acid (2- 339
chloro-phenyl)-amide 128 1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic
acid (1- 387 ethyl-2-methyl-1H-benzoimidazol-5-yl)-amide 129
1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic acid [4-(6- 452
methyl-benzothiazol-2-yl)-phenyl]-amide 130
1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic acid (2- 411
methoxy-biphenyl-4-yl)-amide 131
1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic acid (1H- 345
indazol-6-yl)-amide 132 1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic
acid 305 phenylamide 133
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid 430
(3-diethylcarbamoyl-phenyl)-amide 134
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid 491
[4-(5-methyl-isoxazol-3-ylsulfamoyl)-pheny]-amide 135
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid 365
(2-chloro-phenyl)-amide 136
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid 413
(1-ethyl-2-methyl-1H-benzoimidazol-5-yl)-amide 137
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid 478
[4-(6-methyl-benzothiazol-2-yl)-phenyl]-amide 138
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid 437
(2-methoxy-biphenyl-4-yl)-amide 139
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid 371
(1H-indazol-6-yl)-amide 140
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid 331
phenylamide 141
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 379 carboxylic
acid m-tolylamide 142
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 395 carboxylic
acid (3-methoxy-phenyl)-amide 143
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 379 carboxylic
acid benzylamide 144
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 393 carboxylic
acid benzyl-methyl-amide 145
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 409 carboxylic
acid 4-methoxy-benzylamide 146
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 424 carboxylic
acid 3-nitro-benzylamide 147
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 393 carboxylic
acid 3-methyl-benzylamide 148
2-{[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole- 527
4-carbonyl]-amino}-3-phenyl-propionic acid benzyl ester 149
2-{[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole- 451
4-carbonyl]-amino}-3-phenyl-propionic acid methyl ester 150
2-{[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole- 493
4-carbonyl]-amino}-3-phenyl-propionic acid tert-butyl ester 151
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 429 carboxylic
acid (2-cyclohexyl-1-hydroxymethyl-ethyl)- amide 152
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 390 carboxylic
acid (3-cyano-phenyl)-amide 153
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 422 carboxylic
acid 4-dimethylamino-benzylamide 154
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 443 carboxylic
acid (3-methanesulfonyl-phenyl)-amide 155
4-{[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole- 437
4-carbonyl]-amino}-benzoic acid ethyl ester 156
3-Phenyl-2-[(1-phenyl-5-propyl-1H-pyrazole-4-carbonyl)- 467
amino]-propionic acid benzyl ester 157
3-Phenyl-2-[(1-phenyl-5-propyl-1H-pyrazole-4-carbonyl)- 391
amino]-propionic acid methyl ester 158
3-Phenyl-2-[(1-phenyl-5-propyl-1H-pyrazole-4-carbonyl)- 433
amino]-propionic acid tert-butyl ester 159
1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic acid (2- 369
cyclohexyl-1-hydroxymethyl-ethyl)-amide 160
1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic acid (3- 330
cyano-phenyl)-amide 161 1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic
acid 4- 362 dimethylamino-benzylamide 162
1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic acid (3- 383
methanesulfonyl-phenyl)-amide 163
4-[(1-Phenyl-5-propyl-1H-pyrazole-4-carbonyl)-amino]- 377 benzoic
acid ethyl ester 164
3-Phenyl-2-[(1-phenyl-5-trifluoromethyl-1H-pyrazole-4- 493
carbonyl)-amino]-propionic acid benzyl ester 165
3-Phenyl-2-[(1-phenyl-5-trifluoromethyl-1H-pyrazole-4- 417
carbonyl)-amino]-propionic acid methyl ester 166
3-Phenyl-2-[(1-phenyl-5-trifluoromethyl-1H-pyrazole-4- 459
carbonyl)-amino]-propionic acid tert-butyl ester 167
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid 395
(2-cyclohexyl-1-hydroxymethyl-ethyl)-amide 168
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid 356
(3-cyano-phenyl)-amide 169
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid 388
4-dimethylamino-benzylamide 170
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid 409
(3-methanesulfonyl-phenyl)-amide 171
4-[(1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carbonyl)- 403
amino]-benzoic acid ethyl ester 172
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 465 carboxylic
acid 2-fluoro-5-trifluoromethyl-benzylamide 173
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 461 carboxylic
acid [2-(3-trifluoromethyl-phenyl)-ethyl]- amide 174
[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4-yl]- 473
(7-trifluoromethyl-3,4-dihydro-2H-quinolin-1-yl)- methanone 175
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 463 carboxylic
acid (3-trifluoromethyl-benzyloxy)-amide 176
5-Methyl-1-phenyl-1H-pyrazole-4-carboxylic acid benzylamide 291 177
5-Methyl-1-phenyl-1H-pyrazole-4-carboxylic acid tert- 257
butylamide 178 5-Methyl-1-phenyl-1H-pyrazole-4-carboxylic acid 305
phenethyl-amide 179 5-Methyl-1-phenyl-1H-pyrazole-4-carboxylic acid
297 cyclohexylmethyl-amide 180
5-Methyl-1-phenyl-1H-pyrazole-4-carboxylic acid 269
cyclopentylamide 181 5-Methyl-1-phenyl-1H-pyrazole-4-carboxylic
acid 367 (biphenyl-3-ylmethyl)-amide 182
5-Methyl-1-phenyl-1H-pyrazole-4-carboxylic acid 3,5- 427
bis-trifluoromethyl-benzylamide 183
5-Methyl-1-phenyl-1H-pyrazole-4-carboxylic acid 3- 359
trifluoromethyl-benzylamide 184
5-Methyl-1-phenyl-1H-pyrazole-4-carboxylic acid 335
(benzo[1,3]dioxol-5-ylmethyl)-amide 185
5-Methyl-1-phenyl-1H-pyrazole-4-carboxylic acid 3,4- 359
dichloro-benzylamide 186
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 461 carboxylic
acid methyl-(3-trifluoromethyl-benzyl)-amide 187
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 475 carboxylic
acid ethyl-(3-trifluoromethyl-benzyl)-amide 188
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 437 carboxylic
acid benzo[1,3]dioxol-5-ylmethyl-methyl-amide 189
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 451 carboxylic
acid benzo[1,3]dioxol-5-ylmethyl-ethyl-amide 190
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 399 carboxylic
acid methyl-thiophen-2-ylmethyl-amide 191
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 413 carboxylic
acid ethyl-thiophen-2-ylmethyl-amide 192
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 461 carboxylic
acid methyl-(4-trifluoromethyl-benzyl)-amide 193
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 475 carboxylic
acid ethyl-(4-trifluoromethyl-benzyl)-amide 194
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 494 carboxylic
acid benzo[1,3]dioxol-5-ylmethyl-(2- dimethylamino-ethyl)-amide 195
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 518 carboxylic
acid (2-dimethylamino-ethyl)-(3- trifluoromethyl-benzyl)-amide 196
1-(2-Nitro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 390 carboxylic
acid benzylamide 197
1-(6-Ethoxy-pyridazin-3-yl)-5-trifluoromethyl-1H- 391
pyrazole-4-carboxylic acid benzylamide 198
1-Benzothiazol-2-yl-5-trifluoromethyl-1H-pyrazole-4- 402 carboxylic
acid benzylamide 199
1-(4-Nitro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 390 carboxylic
acid benzylamide 200
1-(4-Methoxy-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 375
carboxylic acid benzylamide 201
1-(2,5-Dichloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 413
carboxylic acid benzylamide 202
5-Trifluoromethyl-1-(4-trifluoromethyl-phenyl)-1H- 413
pyrazole-4-carboxylic acid benzylamide 203
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid 345
benzylamide 204 1-(2-Nitro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
356 carboxylic acid tert-butylamide 205
1-(6-Chloro-pyridazin-3-yl)-5-trifluoromethyl-1H- 347
pyrazole-4-carboxylic acid tert-butylamide 206
1-Benzothiazol-2-yl-5-trifluoromethyl-1H-pyrazole-4- 368 carboxylic
acid tert-butylamide 207
1-(4-Nitro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 356 carboxylic
acid tert-butylamide 208
1-(4-Methoxy-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 341
carboxylic acid tert-butylamide 209
1-(2,5-Dichloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 379
carboxylic acid tert-butylamide 210
5-Trifluoromethyl-1-(4-trifluoromethyl-phenyl)-1H- 379
pyrazole-4-carboxylic acid tert-butylamide 211
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid 311
tert-butylamide 212
1-(2-Nitro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 404 carboxylic
acid phenethyl-amide 213
1-(6-Chloro-pyridazin-3-yl)-5-trifluoromethyl-1H- 395
pyrazole-4-carboxylic acid phenethyl-amide 214
1-Benzothiazol-2-yl-5-trifluoromethyl-1H-pyrazole-4- 416 carboxylic
acid phenethyl-amide 215
1-(4-Nitro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 404 carboxylic
acid phenethyl-amide 216
1-(4-Methoxy-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 389
carboxylic acid phenethyl-amide 217
1-(2,5-Dichloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 427
carboxylic acid phenethyl-amide 218
5-Trifluoromethyl-1-(4-trifluoromethyl-phenyl)-1H- 427
pyrazole-4-carboxylic acid phenethyl-amide 219
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid 359
phenethyl-amide 220
1-(2-Nitro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 396 carboxylic
acid cyclohexylmethyl-amide 221
1-(6-Chloro-pyridazin-3-yl)-5-trifluoromethyl-1H- 387
pyrazole-4-carboxylic acid cyclohexylmethyl-amide 222
1-Benzothiazol-2-yl-5-trifluoromethyl-1H-pyrazole-4- 408 carboxylic
acid cyclohexylmethyl-amide 223
1-(4-Nitro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 396 carboxylic
acid cyclohexylmethyl-amide 224
1-(4-Methoxy-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 381
carboxylic acid cyclohexylmethyl-amide 225
1-(2,5-Dichloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 419
carboxylic acid cyclohexylmethyl-amide 226
5-Trifluoromethyl-1-(4-trifluoromethyl-phenyl)-1H- 419
pyrazole-4-carboxylic acid cyclohexylmethyl-amide 227
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid 351
cyclohexylmethyl-amide 228
1-(2-Nitro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 368 carboxylic
acid cyclopentylamide 229
1-(6-Chloro-pyridazin-3-yl)-5-trifluoromethyl-1H- 359
pyrazole-4-carboxylic acid cyclopentylamide 230
1-Benzothiazol-2-yl-5-trifluoromethyl-1H-pyrazole-4- 380 carboxylic
acid cyclopentylamide 231
1-(4-Nitro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 368 carboxylic
acid cyclopentylamide 232
1-(4-Methoxy-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 353
carboxylic acid cyclopentylamide 233
1-(2,5-Dichloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 391
carboxylic acid cyclopentylamide 234
5-Trifluoromethyl-1-(4-trifluoromethyl-phenyl)-1H- 391
pyrazole-4-carboxylic acid cyclopentylamide 235
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid 323
cyclopentylamide 236
1-(2-Nitro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 466 carboxylic
acid (biphenyl-3-ylmethyl)-amide 237
1-(6-Chloro-pyridazin-3-yl)-5-trifluoromethyl-1H- 457
pyrazole-4-carboxylic acid (biphenyl-3-ylmethyl)-amide 238
1-Benzothiazol-2-yl-5-trifluoromethyl-1H-pyrazole-4- 478 carboxylic
acid (biphenyl-3-ylmethyl)-amide 239
1-(4-Nitro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 466 carboxylic
acid (biphenyl-3-ylmethyl)-amide
240 1-(4-Methoxy-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 451
carboxylic acid (biphenyl-3-ylmethyl)-amide 241
1-(2,5-Dichloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 489
carboxylic acid (biphenyl-3-ylmethyl)-amide 242
5-Trifluoromethyl-1-(4-trifluoromethyl-phenyl)-1H- 489
pyrazole-4-carboxylic acid (biphenyl-3-ylmethyl)-amide 243
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid 421
(biphenyl-3-ylmethyl)-amide 244
1-(2-Nitro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 526 carboxylic
acid 3,5-bis-trifluoromethyl-benzylamide 245
1-(6-Chloro-pyridazin-3-yl)-5-trifluoromethyl-1H- 517
pyrazole-4-carboxylic acid 3,5-bis-trifluoromethyl-benzylamide 246
1-Benzothiazol-2-yl-5-trifluoromethyl-1H-pyrazole-4- 538 carboxylic
acid 3,5-bis-trifluoromethyl-benzylamide 247
1-(4-Nitro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 526 carboxylic
acid 3,5-bis-trifluoromethyl-benzylamide 248
1-(4-Methoxy-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 511
carboxylic acid 3,5-bis-trifluoromethyl-benzylamide 249
1-(2,5-Dichloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 549
carboxylic acid 3,5-bis-trifluoromethyl-benzylamide 250
5-Trifluoromethyl-1-(4-trifluoromethyl-phenyl)-1H- 549
pyrazole-4-carboxylic acid 3,5-bis-trifluoromethyl- benzylamide 251
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid 481
3,5-bis-trifluoromethyl-benzylamide 252
1-(2-Nitro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 458 carboxylic
acid 3-trifluoromethyl-benzylamide 253
1-(6-Chloro-pyridazin-3-yl)-5-trifluoromethyl-1H- 449
pyrazole-4-carboxylic acid 3-trifluoromethyl-benzylamide 254
1-Benzothiazol-2-yl-5-trifluoromethyl-1H-pyrazole-4- 470 carboxylic
acid 3-trifluoromethyl-benzylamide 255
1-(4-Nitro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 458 carboxylic
acid 3-trifluoromethyl-benzylamide 256
1-(4-Methoxy-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 443
carboxylic acid 3-trifluoromethyl-benzylamide 257
1-(2,5-Dichloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 481
carboxylic acid 3-trifluoromethyl-benzylamide 258
5-Trifluoromethyl-1-(4-trifluoromethyl-phenyl)-1H- 481
pyrazole-4-carboxylic acid 3-trifluoromethyl-benzylamide 259
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid 413
3-trifluoromethyl-benzylamide 260
1-(2-Nitro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 434 carboxylic
acid (benzo[1,3]dioxol-5-ylmethyl)-amide 261
1-(6-Chloro-pyridazin-3-yl)-5-trifluoromethyl-1H- 425
pyrazole-4-carboxylic acid (benzo[1,3]dioxol-5- ylmethyl)-amide 262
1-Benzothiazol-2-yl-5-trifluoromethyl-1H-pyrazole-4- 446 carboxylic
acid (benzo[1,3]dioxol-5-ylmethyl)-amide 263
1-(4-Nitro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 434 carboxylic
acid (benzo[1,3]dioxol-5-ylmethyl)-amide 264
1-(4-Methoxy-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 419
carboxylic acid (benzo[1,3]dioxol-5-ylmethyl)-amide 265
1-(2,5-Dichloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 457
carboxylic acid (benzo[1,3]dioxol-5-ylmethyl)-amide 266
5-Trifluoromethyl-1-(4-trifluoromethyl-phenyl)-1H- 457
pyrazole-4-carboxylic acid (benzo[1,3]dioxol-5- ylmethyl)-amide 267
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid 389
(benzo[1,3]dioxol-5-ylmethyl)-amide 268
1-(2-Nitro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 458 carboxylic
acid 3,4-dichloro-benzylamide 269
1-(6-Chloro-pyridazin-3-yl)-5-trifluoromethyl-1H- 449
pyrazole-4-carboxylic acid 3,4-dichloro-benzylamide 270
1-Benzothiazol-2-yl-5-trifluoromethyl-1H-pyrazole-4- 470 carboxylic
acid 3,4-dichloro-benzylamide 271
1-(4-Nitro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 458 carboxylic
acid 3,4-dichloro-benzylamide 272
1-(4-Methoxy-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 443
carboxylic acid 3,4-dichloro-benzylamide 273
1-(2,5-Dichloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 481
carboxylic acid 3,4-dichloro-benzylamide 274
5-Trifluoromethyl-1-(4-trifluoromethyl-phenyl)-1H- 481
pyrazole-4-carboxylic acid 3,4-dichloro-benzylamide 275
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid 413
3,4-dichloro-benzylamide 276
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 367 carboxylic
acid pyrazin-2-ylamide 277
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 435 carboxylic
acid (4,6-dichloro-pyrimidin-2-yl)-amide 278
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 383 carboxylic
acid (3-fluoro-phenyl)-amide 279
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 410 carboxylic
acid (3-nitro-phenyl)-amide 280
5,6-Dichloro-3-{[1-(4-chloro-phenyl)-5-trifluoromethyl- 493
1H-pyrazole-4-carbonyl]-amino}-pyrazine-2-carboxylic acid methyl
ester 281 1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 385
carboxylic acid (2-cyclopentyl-ethyl)-amide 282
1,3,5-Trimethyl-1H-pyrazole-4-carboxylic acid 243 benzylamide 283
1,3,5-Trimethyl-1H-pyrazole-4-carboxylic acid tert- 209 butylamide
284 1,3,5-Trimethyl-1H-pyrazole-4-carboxylic acid phenethyl- 257
amide 285 1,3,5-Trimethyl-1H-pyrazole-4-carboxylic acid 249
cyclohexylmethyl-amide 286 1,3,5-Trimethyl-1H-pyrazole-4-carboxylic
acid 221 cyclopentylamide 287
1,3,5-Trimethyl-1H-pyrazole-4-carboxylic acid (biphenyl- 319
3-ylmethyl)-amide 288 1,3,5-Trimethyl-1H-pyrazole-4-carboxylic acid
3,5-bis- 379 trifluoromethyl-benzylamide 289
1,3,5-Trimethyl-1H-pyrazole-4-carboxylic acid 3- 311
trifluoromethyl-benzylamide 290
1,3,5-Trimethyl-1H-pyrazole-4-carboxylic acid 287
(benzo[1,3]dioxol-5-ylmethyl)-amide 291
1,3,5-Trimethyl-1H-pyrazole-4-carboxylic acid 3,4- 311
dichloro-benzylamide 292
[1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazol-4-yl]- 327
pyrrolidin-1-yl-methanone 293
[1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazol-4-yl]- 410
(2-pyrrolidin-1-ylmethyl-pyrrolidin-1-yl)-methanone 294
[1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazol-4-yl]- 419
(4-pyridin-2-yl-piperazin-1-yl)-methanone 295
(4-Benzo[1,3]dioxol-5-ylmethyl-piperazin-1-yl)-[1-(4- 476
fluoro-phenyl)-5-trifluoromethyl-1H-pyrazol-4-yl]- methanone 296
1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 393 carboxylic
acid 4-methoxy-benzylamide 297
1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 423 carboxylic
acid [2-(4-methoxy-phenoxy)-ethyl]-amide 298
1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 449 carboxylic
acid 3-fluoro-5-trifluoromethyl-benzylamide 299
[1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazol-4-yl]- 356
(4-methyl-piperazin-1-yl)-methanone 300
1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 403 carboxylic
acid (1,2,3,4-tetrahydro-naphthalen-1-yl)- amide 301
1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 433 carboxylic
acid [cyclopropyl-(4-methoxy-phenyl)- methyl]-amide 302
1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 447 carboxylic
acid (2,3-dihydro-benzo[d]imidazo[2,1- b]thiazol-6-yl)-amide 303
2-{[1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 511
carbonyl]-amino}-3-phenyl-propionic acid benzyl ester 304
4-{[1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 421
carbonyl]-amino}-benzoic acid ethyl ester 305
1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 427 carboxylic
acid (3-methanesulfonyl-phenyl)-amide 306
1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 413 carboxylic
acid (2-cyclohexyl-1-hydroxymethyl-ethyl)- amide 307
1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 369 carboxylic
acid (thiophen-2-ylmethyl)-amide 308
1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 353 carboxylic
acid (furan-2-ylmethyl)-amide 309
1-[1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 384
carbonyl]-piperidine-3-carboxylic acid amide 310
1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 389 carboxylic
acid (2-phenyl-cyclopropyl)-amide 311
[1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazol-4-yl]- 357
(3-hydroxy-piperidin-1-yl)-methanone 312
4-Phenyl-1-(1-phenyl-5-propyl-1H-pyrazole-4-carbonyl)- 398
piperidine-4-carbonitrile 313
1-(5-tert-Butyl-2-methyl-2H-pyrazole-3-carbonyl)-4- 350
phenyl-piperidine-4-carbonitrile 314
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 457 carboxylic
acid (3-methanesulfonyl-phenyl)-methyl-amide 315
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 461 carboxylic
acid [2-(3,4-dichloro-phenyl)-ethyl]-amide 316
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 303 carboxylic
acid methylamide 317
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 317 carboxylic
acid dimethylamide 318
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 407 carboxylic
acid (3-acetyl-phenyl)-amide 319
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 487 carboxylic
acid (5-ethanesulfonyl-2-methoxy-phenyl)- amide 320
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 443 carboxylic
acid (4-methanesulfonyl-phenyl)-amide 321
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 453 carboxylic
acid (1,1-dioxo-1H-1lambda*6*- benzo[b]thiophen-6-yl)-amide 322
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 411 carboxylic
acid [2-(2-fluoro-phenyl)-ethyl]-amide 323
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 411 carboxylic
acid [2-(3-fluoro-phenyl)-ethyl]-amide 324
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 427 carboxylic
acid [2-(3-chloro-phenyl)-ethyl]-amide 325
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 427 carboxylic
acid [2-(4-chloro-phenyl)-ethyl]-amide 326
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 461 carboxylic
acid [2-(2,6-dichloro-phenyl)-ethyl]-amide 327
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 400 carboxylic
acid (1-ethyl-pyrrolidin-2-ylmethyl)-amide 328
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 400 carboxylic
acid (1-ethyl-pyrrolidin-2-ylmethyl)-amide 329
5-Chloro-1-methyl-1H-pyrazole-4-carboxylic acid [2-(3,4- 323
dimethoxy-phenyl)-ethyl]-amide 330
(5-Chloro-1-methyl-1H-pyrazol-4-yl)-(4-methyl- 242
piperazin-1-yl)-methanone 331
5-Chloro-1-methyl-1H-pyrazole-4-carboxylic acid (1- 257
methyl-hexyl)-amide 332 5-Chloro-1-methyl-1H-pyrazole-4-carboxylic
acid 243 (tetrahydro-furan-2-ylmethyl)-amide 333
5-Chloro-1-methyl-1H-pyrazole-4-carboxylic acid (2- 264
pyridin-2-yl-ethyl)-amide 334
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic 427 acid
[2-(3,4-dimethoxy-phenyl)-ethyl]-amide 335
[1-(4-Chloro-phenyl)-5-propyl-1H-pyrazol-4-yl]-(4- 346
methyl-piperazin-1-yl)-methanone 336
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic 361 acid
(1-methyl-hexyl)-amide 337
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic 347 acid
(tetrahydro-furan-2-ylmethyl)-amide 338
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic 368 acid
(2-pyridin-2-yl-ethyl)-amide 339
5-Chloro-1-methyl-1H-pyrazole-4-carboxylic acid ethyl- 278
pyridin-4-ylmethyl-amide 340
5-Chloro-1-methyl-1H-pyrazole-4-carboxylic acid benzyl- 291
isopropyl-amide 341 5-Chloro-1-methyl-1H-pyrazole-4-carboxylic acid
(1- 332 benzyl-pyrrolidin-3-yl)-methyl-amide 342
5-Chloro-1-methyl-1H-pyrazole-4-carboxylic acid (3- 272
diethylamino-propyl)-amide 343
5-Chloro-1-methyl-1H-pyrazole-4-carboxylic acid 2,4- 309
dimethoxy-benzylamide 344
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic 382 acid
ethyl-pyridin-4-ylmethyl-amide 345
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic 395 acid
benzyl-isopropyl-amide 346
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic 436 acid
(1-benzyl-pyrrolidin-3-yl)-methyl-amide 347
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic 376 acid
(3-diethylamino-propyl)-amide 348
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic 413 acid
2,4-dimethoxy-benzylamide 349
5-Chloro-1-methyl-1H-pyrazole-4-carboxylic acid benzyl- 263
methyl-amide 350 5-Chloro-1-methyl-1H-pyrazole-4-carboxylic acid
(3,4- 271 difluoro-phenyl)-amide 351
5-Chloro-1-methyl-1H-pyrazole-4-carboxylic acid (3- 303
trifluoromethyl-phenyl)-amide 352
5-Chloro-1-methyl-1H-pyrazole-4-carboxylic acid methyl- 250
pyridin-2-yl-amide 353 5-Chloro-1-methyl-1H-pyrazole-4-carboxylic
acid (3- 277 phenyl-propyl)-amide 354
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic 367 acid
benzyl-methyl-amide 355
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic 375 acid
(3,4-difluoro-phenyl)-amide 356
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic 407 acid
(3-trifluoromethyl-phenyl)-amide 357
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic 354 acid
methyl-pyridin-2-yl-amide 358
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic 381 acid
(3-phenyl-propyl)-amide 359
5-Chloro-1-methyl-1H-pyrazole-4-carboxylic acid (2- 264
pyridin-4-yl-ethyl)-amide
360 5-Chloro-1-methyl-1H-pyrazole-4-carboxylic acid 293
(benzo[1,3]dioxol-5-ylmethyl)-amide 361
5-Chloro-1-methyl-1H-pyrazole-4-carboxylic acid 263 phenethyl-amide
362 5-Chloro-1-methyl-1H-pyrazole-4-carboxylic acid (2- 253
ethyl-2H-pyrazol-3-yl)-amide 363
5-Chloro-1-methyl-1H-pyrazole-4-carboxylic acid [2-(3,4- 331
dichloro-phenyl)-ethyl]-amide 364
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic 368 acid
(2-pyridin-4-yl-ethyl)-amide 365
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic 397 acid
(benzo[1,3]dioxol-5-ylmethyl)-amide 366
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic 367 acid
phenethyl-amide 367
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic 357 acid
(2-ethyl-2H-pyrazol-3-yl)-amide 368
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic 435 acid
[2-(3,4-dichloro-phenyl)-ethyl]-amide 369
5-Chloro-1-methyl-1H-pyrazole-4-carboxylic acid [2-(3- 331
trifluoromethyl-phenyl)-ethyl]-amide 370
5-Chloro-1-methyl-1H-pyrazole-4-carboxylic acid (2- 269
thiophen-2-yl-ethyl)-amide 371
5-Chloro-1-methyl-1H-pyrazole-4-carboxylic acid [2-(4- 297
chloro-phenyl)-ethyl]-amide 372
5-Chloro-1-methyl-1H-pyrazole-4-carboxylic acid 3- 317
trifluoromethyl-benzylamide 373
5-Chloro-1-methyl-1H-pyrazole-4-carboxylic acid (3- 313
methanesulfonyl-phenyl)-amide 374
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic 435 acid
[2-(3-trifluoromethyl-phenyl)-ethyl]-amide 375
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic 373 acid
(2-thiophen-2-yl-ethyl)-amide 376
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic 401 acid
[2-(4-chloro-phenyl)-ethyl]-amide 377
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic 421 acid
3-trifluoromethyl-benzylamide 378
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic 417 acid
(3-methanesulfonyl-phenyl)-amide 379
5-Chloro-1-methyl-1H-pyrazole-4-carboxylic acid [2-(1H- 302
indol-3-yl)-ethyl]-amide 380
5-Chloro-1-methyl-1H-pyrazole-4-carboxylic acid [2-(3- 281
fluoro-phenyl)-ethyl]-amide 381
5-Chloro-1-methyl-1H-pyrazole-4-carboxylic acid [2-(2- 281
fluoro-phenyl)-ethyl]-amide 382
5-Chloro-1-methyl-1H-pyrazole-4-carboxylic acid (1- 270
ethyl-pyrrolidin-2-ylmethyl)-amide 383
5-Chloro-1-methyl-1H-pyrazole-4-carboxylic acid (1- 270
ethyl-pyrrolidin-2-ylmethyl)-amide 384
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic 406 acid
[2-(1H-indol-3-yl)-ethyl]-amide 385
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic 385 acid
[2-(3-fluoro-phenyl)-ethyl]-amide 386
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic 385 acid
[2-(2-fluoro-phenyl)-ethyl]-amide 387
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic 374 acid
(1-ethyl-pyrrolidin-2-ylmethyl)-amide 388
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic 374 acid
(1-ethyl-pyrrolidin-2-ylmethyl)-amide 389
5-Chloro-1-methyl-1H-pyrazole-4-carboxylic acid 2,6- 309
dimethoxy-benzylamide 390
5-Chloro-1-methyl-1H-pyrazole-4-carboxylic acid [2-(3- 297
chloro-phenyl)-ethyl]-amide 391
5-Chloro-1-methyl-1H-pyrazole-4-carboxylic acid [2-(3,5- 323
dimethoxy-phenyl)-ethyl]-amide 392
5-Chloro-1-methyl-1H-pyrazole-4-carboxylic acid (5- 270
chloro-pyridin-2yl)-amide 393
5-Chloro-1-methyl-1H-pyrazole-4-carboxylic acid (2- 277
phenyl-propyl)-amide 394
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic 413 acid
2,6-dimethoxy-benzylamide 395
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic 401 acid
[2-(3-chloro-phenyl)-ethyl]-amide 396
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic 427 acid
[2-(3,5-dimethoxy-phenyl)-ethyl]-amide 397
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic 374 acid
(5-chloro-pyridin-2-yl)-amide 398
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic 381 acid
(2-phenyl-propyl)-amide 399
5-Chloro-1-methyl-1H-pyrazole-4-carboxylic acid [2-(4- 281
fluoro-phenyl)-ethyl]-amide 400
5-Chloro-1-methyl-1H-pyrazole-4-carboxylic acid [2-(2,4- 331
dichloro-phenyl)-ethyl]-amide 401
5-Chloro-1-methyl-1H-pyrazole-4-carboxylic acid 325
(biphenyl-3-ylmethyl)-amide 402
5-Chloro-1-methyl-1H-pyrazole-4-carboxylic acid 236
pyridin-4-ylamide 403 5-Chloro-1-methyl-1H-pyrazole-4-carboxylic
acid (3- 375 benzenesulfonyl-phenyl)-amide 404
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic 385 acid
[2-(4-fluoro-phenyl)-ethyl]-amide 405
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic 435 acid
[2-(2,4-dichloro-phenyl)-ethyl]-amide 406
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic 429 acid
(biphenyl-3-ylmethyl)-amide 407
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic 340 acid
pyridin-4-ylamide 408
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic 479 acid
(3-benzenesulfonyl-phenyl)-amide 409
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 425 carboxylic
acid [2-(3,4-dihydroxy-phenyl)-ethyl]-amide 410
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 381 carboxylic
acid (3-hydroxy-phenyl)-amide 411
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 411 carboxylic
acid [2-(4-fluoro-phenyl)-ethyl]-amide 412
5-Trifluoromethyl-1-(4-trifluoromethyl-phenyl)-1H- 495
pyrazole-4-carboxylic acid [2-(2,4-dichloro-phenyl)- ethyl]-amide
413 1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 461
carboxylic acid (2-fluoro-5-methanesulfonyl-phenyl)- amide 414
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 427 carboxylic
acid [2-(2-chloro-phenyl)-ethyl]-amide 415
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 409 carboxylic
acid [2-(4-hydroxy-phenyl)-ethyl]-amide 416
1-(3-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 447 carboxylic
acid 3-trifluoromethyl-benzylamide 417
1-(4-Nitro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 454 carboxylic
acid (3-methanesulfonyl-phenyl)-amide 418
1-(4-Amino-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 424 carboxylic
acid (3-methanesulfonyl-phenyl)-amide 419
1-(2,5-Dichloro-phenyl)-1H-pyrazole-4-carboxylic acid 393
[2-(3-chloro-phenyl)-ethyl]-amide 420
1-(2-Nitro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 438 carboxylic
acid [2-(3-chloro-phenyl)-ethyl]-amide 421
1-Benzothiazol-2-yl-5-trifluoromethyl-1H-pyrazole-4- 450 carboxylic
acid [2-(3-chloro-phenyl)-ethyl]-amide 422
1-(4-Nitro-phenyl)-5-trifiuoromethyl-1H-pyrazole-4- 438 carboxylic
acid [2-(3-chloro-phenyl)-ethyl]-amide 423
1-(4-Amino-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 408 carboxylic
acid [2-(3-chloro-phenyl)-ethyl]-amide 424
1-(4-Guanidino-phenyl)-5-trifiuoromethyl-1H-pyrazole-4- 466
carboxylic acid (3-methanesulfonyl-phenyl)-amide 425
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid 393
[2-(2-chloro-phenyl)-ethyl]-amide 426
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid 393
[2-(3-chloro-phenyl)-ethyl]-amide 427
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid 393
[2-(4-chloro-phenyl)-ethyl]-amide 428
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid 427
[2-(2,4-dichloro-phenyl)-ethyl]-amide 429
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid 427
[2-(3,4-dichloro-phenyl)-ethyl]-amide 430
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid 427 [2
(2,6-dichloro-phenyl)-ethyl]-amide 431
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid 377
[2-(2-fluoro-phenyl)-ethyl]-amide 432
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid 377
[2-(3-fluoro-phenyl)-ethyl]-amide 433
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid 377
[2-(4-fluoro-phenyl)-ethyl]-amide 434
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid 427
[2-(3-trifluoromethyl-phenyl)-ethyl]-amide 435
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid 387
[2-(4-ethyl-phenyl)-ethyl]-amide 436
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid 419
[2-(3,5-dimethoxy-phenyl)-ethyl]-amide 437
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid 419
[2-(3,4-dimethoxy-phenyl)-ethyl]-amide 438
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid 365
(2-thiophen-2-yl-ethyl)-amide 439
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid 363
4-fluoro-benzylamide 440
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid 379
2-chloro-benzylamide 441
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid 379
4-chloro-benzylamide 442
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid 359
3-methyl-benzylamide 443
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid 359
4-methyl-benzylamide 444
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid 413
4-trifluoromethyl-benzylamide 445
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid 431
3-fluoro-5-trifluoromethyl-benzylamide 446
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 409 carboxylic
acid [2-(3-hydroxy-phenyl)-ethyl]-amide 447
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid 375
[2-(3-hydroxy-phenyl)-ethyl]-amide 448
1-(3-Chloro-phenyl)-1H-pyrazole-4-carboxylic acid (3- 375
methanesulfonyl-phenyl)-amide 449
1-(3-Chloro-phenyl)-1H-pyrazole-4-carboxylic acid [2-(3- 359
chloro-phenyl)-ethyl]-amide 450
1-(3-Chloro-phenyl)-1H-pyrazole-4-carboxylic acid [2- 393
(2,6-dichloro-phenyl)-ethyl]-amide 451
1-(4-Chloro-phenyl)-1H-pyrazole-4-carboxylic acid (3- 375
methanesulfonyl-phenyl)-amide 452
1-(4-Chloro-phenyl)-1H-pyrazole-4-carboxylic acid [2-(3- 359
chloro-phenyl)-ethyl]-amide 453
1-(4-Chloro-phenyl)-1H-pyrazole-4-carboxylic acid [2- 393
(2,6-dichloro-phenyl)-ethyl]-amide 454
1-Benzyl-1H-pyrazole-4-carboxylic acid (3- 355
methanesulfonyl-phenyl)-amide 455 1-Benzyl-1H-pyrazole-4-carboxylic
acid [2-(3-chloro- 339 phenyl)-ethyl]-amide 456
1-Benzyl-1H-pyrazole-4-carboxylic acid [2-(2,6-dichloro- 373
phenyl)-ethyl]-amide 457 1-p-Tolyl-1H-pyrazole-4-carboxylic acid
(3- 355 methanesulfonyl-phenyl)-amide 458
1-p-Tolyl-1H-pyrazole-4-carboxylic acid [2-(3-chloro- 339
phenyl)-ethyl]-amide 459 1-p-Tolyl-1H-pyrazole-4-carboxylic acid
[2-(2,6-dichloro- 373 phenyl)-ethyl]-amide 460
1-(2-Chloro-phenyl)-1H-pyrazole-4-carboxylic acid (3- 375
methanesulfonyl-phenyl)-amide 461
1-(2-Chloro-phenyl)-1H-pyrazole-4-carboxylic acid [2-(3- 359
chloro-phenyl)-ethyl]-amide 462
1-(2-Chloro-phenyl)-1H-pyrazole-4-carboxylic acid [2- 393
(2,6-dichloro-phenyl)-ethyl]-amide 463
1-(3,4-Dichloro-phenyl)-1H-pyrazole-4-carboxylic acid 409
(3-methanesulfonyl-phenyl)-amide 464
1-(3,4-Dichloro-phenyl)-1H-pyrazole-4-carboxylic acid 393
[2-(3-chloro-phenyl)-ethyl]-amide 465
1-(3,4-Dichloro-phenyl)-1H-pyrazole-4-carboxylic acid 427
[2-(2,6-dichloro-phenyl)-ethyl]-amide 466
1-(4-Bromo-phenyl)-1H-pyrazole-4-carboxylic acid (3- 419
methanesulfonyl-phenyl)-amide 467
1-(4-Bromo-phenyl)-1H-pyrazole-4-carboxylic acid [2-(3- 403
chloro-phenyl)-ethyl]-amide 468
1-(4-Bromo-phenyl)-1H-pyrazole-4-carboxylic acid [2- 437
(2,6-dichloro-phenyl)-ethyl]-amide 469
1-(4-Fluoro-phenyl)-1H-pyrazole-4-carboxylic acid (3- 359
methanesulfonyl-phenyl)-amide 470
1-(4-Fluoro-phenyl)-1H-pyrazole-4-carboxylic acid [2-(3- 343
chloro-phenyl)-ethyl]-amide 471
1-(4-Fluoro-phenyl)-1H-pyrazole-4-carboxylic acid [2- 377
(2,6-dichloro-phenyl)-ethyl]-amide 472
1-(4-Methoxy-phenyl)-1H-pyrazole-4-carboxylic acid (3- 371
methanesulfonyl-phenyl)-amide 473
1-(4-Methoxy-phenyl)-1H-pyrazole-4-carboxylic acid [2- 355
(3-chloro-phenyl)-ethyl]-amide 474
1-(4-Methoxy-phenyl)-1H-pyrazole-4-carboxylic acid [2- 389
(2,6-dichloro-phenyl)-ethyl]-amide 475
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid 391
[2-(3,4-dihydroxy-phenyl)-ethyl]-amide 476
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid 375
[2-(4-hydroxy-phenyl)-ethyl]-amide 477
1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 363 carboxylic
acid benzylamide 478
1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 377 carboxylic
acid phenethyl-amide 479
1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 411 carboxylic
acid [2-(2-chloro-phenyl)-ethyl]-amide 480
1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 411 carboxylic
acid [2-(3-chloro-phenyl)-ethyl]-amide 481
1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 411 carboxylic
acid [2-(4-chloro-phenyl)-ethyl]-amide 482
1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 445 carboxylic
acid [2-(2,4-dichloro-phenyl)-ethyl]-amide 483
1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 445 carboxylic
acid [2-(3,4-dichloro-phenyl)-ethyl]-amide 484
1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 445
carboxylic acid [2-(2,6-dichloro-phenyl)-ethyl]-amide 485
1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 395 carboxylic
acid [2-(2-fluoro-phenyl)-ethyl]-amide 486
1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 395 carboxylic
acid [2-(3-fluoro-phenyl)-ethyl]-amide 487
1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 395 carboxylic
acid [2-(4-fluoro-phenyl)-ethyl]-amide 488
1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 445 carboxylic
acid [2-(3-trifluoromethyl-phenyl)-ethyl]- amide 489
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 433 carboxylic
acid (2-trifluoromethyl-phenyl)-amide 490
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 401 carboxylic
acid (2,4-difluoro-phenyl)-amide 491
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 407 carboxylic
acid (4-isopropyl-phenyl)-amide 492
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 451 carboxylic
acid (2-fluoro-5-trifluoromethyl-phenyl)-amide 493
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 405 carboxylic
acid (2-isopropenyl-phenyl)-amide 494
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 393 carboxylic
acid (4-ethyl-phenyl)-amide 495
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 451 carboxylic
acid (2-fluoro-3-trifluoromethyl-phenyl)-amide 496
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 449 carboxylic
acid (2-trifluoromethoxy-phenyl)-amide 497
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 393 carboxylic
acid (2,5-dimethyl-phenyl)-amide 498
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 419 carboxylic
acid (2,3,4-trifluoro-phenyl)-amide 499
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 383 carboxylic
acid (2-fluoro-phenyl)-amide 500
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 421 carboxylic
acid (4-tert-butyl-phenyl)-amide 501
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 467 carboxylic
acid (2-chloro-5-trifluoromethyl-phenyl)-amide 502
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 433 carboxylic
acid (3-trifluoromethyl-phenyl)-amide 503
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 379 carboxylic
acid o-tolylamide 504
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 393 carboxylic
acid (2,4-dimethyl-phenyl)-amide 505
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 421 carboxylic
acid (2-tert-butyl-phenyl)-amide 506
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 393 carboxylic
acid (2,6-dimethyl-phenyl)-amide 507
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 409 carboxylic
acid (4-ethoxy-phenyl)-amide 508
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 400 carboxylic
acid (2-chloro-pyridin-3-yl)-amide 509
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 433 carboxylic
acid (2,4-dichloro-phenyl)-amide 510
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 441 carboxylic
acid biphenyl-4-ylamide 511
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 413 carboxylic
acid (5-chloro-2-methyl-phenyl)-amide 512
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 399 carboxylic
acid (4-chloro-phenyl)-amide 513
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 390 carboxylic
acid (4-cyano-phenyl)-amide 514
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- carboxylic
acid (3-benzenesulfonyl-phenyl)-amide 515
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 471 carboxylic
acid (4-methoxy-biphenyl-3-yl)-amide 516
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 450 carboxylic
acid (4-morpholin-4-yl-phenyl)-amide 517
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 433 carboxylic
acid (4-trifluoromethyl-phenyl)-amide 518
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 450 carboxylic
acid [4-(ethyl-isopropyl-amino)-phenyl]-amide 519
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 413 carboxylic
acid (2-chloro-5-methyl-phenyl)-amide 520
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 448 carboxylic
acid (2-piperidin-1-yl-phenyl)-amide 521
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 408 carboxylic
acid (4-dimethylamino-phenyl)-amide 522
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 409 carboxylic
acid (5-methoxy-2-methyl-phenyl)-amide 523
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 447 carboxylic
acid (4-methyl-2-oxo-2H-chromen-7-yl)-amide 524
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 429 carboxylic
acid (2-chloro-5-methoxy-phenyl)-amide 525
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 416 carboxylic
acid quinolin-8-ylamide 526
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 430 carboxylic
acid (2-pyrrol-1-yl-phenyl)-amide 527
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 480 carboxylic
acid [2-(1H-indol-2-yl)-phenyl]-amide 528
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 404 carboxylic
acid (3-cyanomethyl-phenyl)-amide 529
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 541 carboxylic
acid [5-chloro-2-(4-chloro-phenylsulfanyl)- phenyl]-amide 530
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 390 carboxylic
acid (2-cyano-phenyl)-amide 531
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 409 carboxylic
acid (4-methoxy-phenyl)-methyl-amide 532
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 395 carboxylic
acid (4-methoxy-phenyl)-amide 533
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 434 carboxylic
acid (5-trifluoromethyl-pyridin-2-yl)-amide 534
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 467 carboxylic
acid (2-chloro-4-trifluoromethyl-phenyl)-amide 535
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 397 carboxylic
acid (5-fluoro-2-methyl-phenyl)-amide 536
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 386 carboxylic
acid (3-methyl-isothiazol-5-yl)-amide 537
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 372 carboxylic
acid thiazol-2-ylamide 538
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 432 carboxylic
acid (5-phenyl-oxazol-2-yl)-amide 539
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 407 carboxylic
acid (1,1-dioxo-tetrahydro-1lambda*6*- thiophen-3-yl)-amide 540
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 402 carboxylic
acid (5-methylsulfanyl-1H-[1,2,4]triazol-3-yl)- amide 541
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 356 carboxylic
acid (1H-[1,2,4]triazol-3-yl)-amide 542
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 441 carboxylic
acid (5-trifluoromethyl-[1,3,4]thiadiazol-2-yl)- amide 543
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 370 carboxylic
acid (3-methyl-isoxazol-5-yl)-amide 544
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 448 carboxylic
acid (4-phenyl-thiazol-2-yl)-amide 545
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 422 carboxylic
acid benzothiazol-2-ylamide 546
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 405 carboxylic
acid (1H-benzoimidazol-2-yl)-amide 547
1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 393 carboxylic
acid 3-methoxy-benzylamide 548
1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 393 carboxylic
acid 2-methoxy-benzylamide 549
1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 377 carboxylic
acid 3-methyl-benzylamide 550
1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 377 carboxylic
acid 4-methyl-benzylamide 551
1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 397 carboxylic
acid 2-chloro-benzylamide 552
1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 431 carboxylic
acid 3,4-dichloro-benzylamide 553
1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 423 carboxylic
acid 2,4-dimethoxy-benzylamide 554
1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 423 carboxylic
acid 2,3-dimethoxy-benzylamide 555
1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 397 carboxylic
acid 4-chloro-benzylamide 556
1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 369 carboxylic
acid cyclohexylmethyl-amide 557
1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 431 carboxylic
acid 2,4-dichloro-benzylamide 558
1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 489 carboxylic
acid 3-iodo-benzylamide 559
1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 381 carboxylic
acid 2-fluoro-benzylamide 560
1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 431 carboxylic
acid 4-trifluoromethyl-benzylamide 561
1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 357 carboxylic
acid (tetrahydro-furan-2-ylmethyl)-amide 562
1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 407 carboxylic
acid (benzo[1,3]dioxol-5-ylmethyl)-amide 563
1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 449 carboxylic
acid 2-fluoro-5-trifluoromethyl-benzylamide 564
1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 431 carboxylic
acid 3-trifluoromethyl-benzylamide 565
1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 499 carboxylic
acid 3,5-bis-trifluoromethyl-benzylamide 566
1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 423 carboxylic
acid 2,6-dimethoxy-benzylamide 567
1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 423 carboxylic
acid 3,5-dimethoxy-benzylamide 568
1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 377 carboxylic
acid (1-phenyl-ethyl)-amide 569
1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 364 carboxylic
acid (pyridin-2-ylmethyl)-amide 570
1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 455 carboxylic
acid [2-(4-bromo-phenyl)-ethyl]amide 571
1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 407 carboxylic
acid [2-(3-methoxy-phenyl)-ethyl]-amide 572
1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 437 carboxylic
acid [2-(3,5-dimethoxy-phenyl)-ethyl]-amide 573
1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 437 carboxylic
acid [2-(3,4-dimethoxy-phenyl)-ethyl]-amide 574
1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 391 carboxylic
acid (2-o-tolyl-ethyl)-amide 575
1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 405 carboxylic
acid [2-(3,4-dimethyl-phenyl)-ethyl]-amide 576
1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 405 carboxylic
acid [2-(2,4-dimethyl-phenyl)-ethyl]-amide 577
1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 405 carboxylic
acid (4-phenyl-butyl)-amide 578
1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 393 carboxylic
acid [2-(4-hydroxy-phenyl)-ethyl]-amide 579
1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 383 carboxylic
acid (2-chloro-phenyl)-amide 580
1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 363 carboxylic
acid o-tolylamide 581
1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 363 carboxylic
acid m-tolylamide 582
1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 379 carboxylic
acid (2-methoxy-phenyl)-amide 583
1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 367 carboxylic
acid (3-fluoro-phenyl)-amide 584
1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 385 carboxylic
acid (2,4-difluoro-phenyl)-amide 585
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 449 carboxylic
acid (3-trifluoromethoxy-phenyl)-amide 586
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid 399
(2-trifluoromethyl-phenyl)-amide 587
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic 407 acid
(2-trifluoromethyl-phenyl)-amide 588
1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic acid (2- 373
trifluoromethyl-phenyl)-amide 589
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid 366
(2-chloro-pyridin-3-yl)-amide 590
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic 374 acid
(2-chloro-pyridin-3-yl)-amide 591
1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic acid (2- 340
chloro-pyridin-3-yl)-amide 592
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid 373
(4-isopropyl-phenyl)-amide 593
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic 381 acid
(4-isopropyl-phenyl)-amide 594
1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic acid (4- 347
isopropyl-phenyl)-amide 595
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid 365
(4-chloro-phenyl)-amide 596
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic 373 acid
(4-chloro-phenyl)-amide 597
1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic acid (4- 339
chloro-phenyl)-amide 598
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid 359
(4-ethyl-phenyl)-amide 599
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic 367 acid
(4-ethyl-phenyl)-amide 600
1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic acid (4- 333
ethyl-phenyl)-amide 601
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid 356
(4-cyano-phenyl)-amide 602
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic 364 acid
(4-cyano-phenyl)-amide 603
1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic acid (4- 330
cyano-phenyl)-amide 604
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid 415
(2-trifluoromethoxy-phenyl)-amide 605
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic 423 acid
(2-trifluoromethoxy-phenyl)-amide 606
1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic acid (2- 389
trifluoromethoxy-phenyl)-amide 607
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid 416
(4-morpholin-4-yl-phenyl)-amide 608
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic 424 acid
(4-morpholin-4-yl-phenyl)-amide 609
1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic acid (4- 390
morpholin-4-yl-phenyl)-amide 610
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid 349
(2-fluoro-phenyl)-amide 611
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic 357 acid
(2-fluoro-phenyl)-amide 612
1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic acid (2- 323
fluoro-phenyl)-amide 613
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid 399
(4-trifluoromethyl-phenyl)-amide 614
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic 407 acid
(4-trifluoromethyl-phenyl)-amide 615
1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic acid (4- 373
trifluoromethyl-phenyl)-amide 616
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid 399
(3-trifluoromethyl-phenyl)-amide 617
1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic acid (3- 373
trifluoromethyl-phenyl)-amide 618
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid 414
(2-piperidin-1-yl-phenyl)-amide 619
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic 422 acid
(2-piperidin-1-yl-phenyl)-amide 620
1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic acid (2- 388
piperidin-1-yl-phenyl)-amide 621
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid 345
o-tolylamide 622
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic 353 acid
o-tolylamide 623 1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic acid o-
319 tolylamide 624
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid 382
quinolin-8-ylamide 625
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic 390 acid
quinolin-8-ylamide 626 1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic
acid 356 quinolin-8-ylamide 627
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid 375
(4-ethoxy-phenyl)-amide 628
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic 383 acid
(4-ethoxy-phenyl)-amide 629
1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic acid (4- 349
ethoxy-phenyl)-amide 630
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid 437
[2-(4-bromo-phenyl)-ethyl]-amide 631
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic 445 acid
[2-(4-bromo-phenyl)-ethyl]-amide 632
1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic acid [2-(4- 411
bromo-phenyl)-ethyl]-amide 633
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid 387
[2-(3,4-dimethyl-phenyl)-ethyl]-amide 634
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic 395 acid
[2-(3,4-dimethyl-phenyl)-ethyl]-amide 635
1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic acid [2-(3,4- 361
dimethyl-phenyl)-ethyl]-amide 636
1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic acid [2-(3- 367
chloro-phenyl)-ethyl]-amide 637
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid 389
[2-(2-methoxy-phenyl)-ethyl]-amide 638
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic 397 acid
[2-(2-methoxy-phenyl)-ethyl]-amide 639
1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic acid [2-(2- 363
methoxy-phenyl)-ethyl]-amide 640
1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic acid [2-(3- 351
fluoro-phenyl)-ethyl]-amide 641
1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic acid [2-(3,4- 401
dichloro-phenyl)-ethyl]-amide 642
1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic acid [2-(4- 367
chloro-phenyl)-ethyl]-amide 643
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic 435 acid
[2-(2,6-dichloro-phenyl)-ethyl]-amide 644
1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic acid [2-(2,6- 401
dichloro-phenyl)-ethyl]-amide 645
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid 389
[2-(3-methoxy-phenyl)-ethyl]-amide 646
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic 397 acid
[2-(3-methoxy-phenyl)-ethyl]-amide 647
1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic acid [2-(3- 363
methoxy-phenyl)-ethyl]-amide 648
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid 373
(2-o-tolyl-ethyl)-amide 649
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic 381 acid
(2-o-tolyl-ethyl)-amide 650
1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic acid (2-o- 347
tolyl-ethyl)-amide 651
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid 375
(2-phenoxy-ethyl)-amide 652
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic 383 acid
(2-phenoxy-ethyl)-amide 653
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid 387
(4-phenyl-butyl)-amide 654
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic 395 acid
(4-phenyl-butyl)-amide 655
1-Phenyl-5-propyl-1H-pyrazole-4-caxboxylic acid (4- 361
phenyl-butyl)-amide 656
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid 385
(1,2,3,4-tetrahydro-naphthalen-1-yl)-amide 657
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic 393 acid
(1,2,3,4-tetrahydro-naphthalen-1-yl)-amide 658
1-Phenyl-5-propyl-1H-pyrazole-4-caxboxylic acid 359
(1,2,3,4-tetrahydro-naphthalen-1-yl)-amide 659
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid 387
[2-(2,4-dimethyl-phenyl)-ethyl]-amide 660
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic 395 acid
[2-(2,4-dimethyl-phenyl)-ethyl]-amide 661
1-Phenyl-5-propyl-1H-pyrazole-4-carboxylic acid [2-(2,4- 361
dimethyl-phenyl)-ethyl]-amide 662
1-Phenyl-5-trifluoromethyl-1H-pyrazole-4-carboxylic acid 371
indan-1-ylamide 663
1-(4-Chloro-phenyl)-5-propyl-1H-pyrazole-4-carboxylic 379 acid
indan-1-ylamide 664
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 471 carboxylic
acid [2-(4-bromo-phenyl)-ethyl]-amide 665
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 423 carboxylic
acid [2-(3-methoxy-phenyl)-ethyl]-amide 666
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 407 carboxylic
acid (2-o-tolyl-ethyl)-amide 667
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 421 carboxylic
acid (4-phenyl-butyl)-amide 668
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 421 carboxylic
acid [2-(2,4-dimethyl-phenyl)-ethyl]-amide 669
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 421 carboxylic
acid [2-(3,4-dimethyl-phenyl)-ethyl]-amide 670
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 423 carboxylic
acid [2-(2-methoxy-phenyl)-ethyl]-amide 671
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 419 carboxylic
acid (1,2,3,4-tetrahydro-naphthalen-1-yl)- amide 672
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 449 carboxylic
acid (2,4,6-triethyl-phenyl)-amide 673
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 407 carboxylic
acid (2-ethyl-6-methyl-phenyl)-amide 674
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 407 carboxylic
acid (2,4,6-trimethyl-phenyl)-amide 675
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 421 carboxylic
acid (2,6-diethyl-phenyl)-amide 676
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 501 carboxylic
acid (2,5-bis-trifluoromethyl-phenyl)-amide 677
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 449 carboxylic
acid (2,6-diisopropyl-phenyl)-amide 678
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 421 carboxylic
acid (2-isopropyl-6-methyl-phenyl)-amide 679
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 494 carboxylic
acid (2,4,6-triethyl-3-nitro-phenyl)-amide 680
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 401 carboxylic
acid (3,4-difluoro-phenyl)-amide 681
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 477 carboxylic
acid (2,5-di-tert-butyl-phenyl)-amide 682
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 455 carboxylic
acid (3-chloro-2,6-diethyl-phenyl)-amide 683
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 447 carboxylic
acid (4-cyclohexyl-phenyl)-amide 684
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 521 carboxylic
acid (2,5-dibromo-phenyl)-amide 685
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 407 carboxylic
acid (2-isopropyl-phenyl)-amide 686
5-Methyl-1-phenyl-1H-pyrazole-4-carboxylic acid 4- 325
chloro-benzylamide 687 5-Methyl-1-phenyl-1H-pyrazole-4-carboxylic
acid 2- 325 chloro-benzylamide 688
5-Methyl-1-phenyl-1H-pyrazole-4-carboxylic acid 2- 309
fluoro-benzylamide 689 5-Methyl-1-phenyl-1H-pyrazole-4-carboxylic
acid 4- 309 fluoro-benzylamide 690
5-Methyl-1-phenyl-1H-pyrazole-4-carboxylic acid (2- 311
chloro-phenyl)-amide 691 5-Methyl-1-phenyl-1H-pyrazole-4-carboxylic
acid (3- 311 chloro-phenyl)-amide 692
5-Methyl-1-phenyl-1H-pyrazole-4-carboxylic acid (4- 311
chloro-phenyl)-amide 693
1-(4-Methoxy-phenyl)-5-methyl-1H-pyrazole-4- 321 carboxylic acid
benzylamide 694 1-(4-Methoxy-phenyl)-5-methyl-1H-pyrazole-4- 335
carboxylic acid phenethyl-amide 695
1-(4-Methoxy-phenyl)-5-methyl-1H-pyrazole-4- 365 carboxylic acid
(benzo[1,3]dioxol-5-ylmethyl)-amide 696
1-(4-Methoxy-phenyl)-5-methyl-1H-pyrazole-4- 355 carboxylic acid
4-chloro-benzylamide 697
1-(4-Methoxy-phenyl)-5-methyl-1H-pyrazole-4- 355 carboxylic acid
2-chloro-benzylamide 698
1-(4-Methoxy-phenyl)-5-methyl-1H-pyrazole-4- 339 carboxylic acid
2-fluoro-benzylamide 699
1-(4-Methoxy-phenyl)-5-methyl-1H-pyrazole-4- 339 carboxylic acid
4-fluoro-benzylamide 700
1-(4-Methoxy-phenyl)-5-methyl-1H-pyrazole-4- 341 carboxylic acid
(2-chloro-phenyl)-amide 701
1-(4-Methoxy-phenyl)-5-methyl-1H-pyrazole-4- 341 carboxylic acid
(3-chloro-phenyl)-amide 702
1-(4-Methoxy-phenyl)-5-methyl-1H-pyrazole-4- 341 carboxylic acid
(4-chloro-phenyl)-amide 703
5-Methyl-1-phenyl-1H-pyrazole-4-carboxylic acid 277 phenylamide 704
5-Methyl-1-phenyl-1H-pyrazole-4-carboxylic acid 292
(pyridin-3-ylmethyl)-amide 705
1-(4-Methoxy-phenyl)-5-methyl-1H-pyrazole-4- 307 carboxylic acid
phenylamide 706 1-(4-Methoxy-phenyl)-5-methyl-1H-pyrazole-4- 322
carboxylic acid (pyridin-3-ylmethyl)-amide 707
1-(4-Fluoro-phenyl)-5-methyl-1H-pyrazole-4-carboxylic 309 acid
benzylamide 708 1-Benzyl-1H-pyrazole-4-carboxylic acid benzylamide
291 709 1-(4-Fluoro-phenyl)-5-methyl-1H-pyrazole-4-carboxylic 341
acid [2-(2-fluoro-phenyl)-ethyl]-amide 710
1-Benzyl-1H-pyrazole-4-carboxylic acid [2-(2-fluoro- 323
phenyl)-ethyl]-amide 711 1-Benzyl-1H-pyrazole-4-carboxylic acid
[2-(2-fluoro- 323 phenyl)-ethyl]-amide 712
1-Benzyl-1H-pyrazole-4-carboxylic acid phenethyl-amide 305 713
1-Benzyl-1H-pyrazole-4-carboxylic acid phenethyl-amide 341 714
1-Benzyl-1H-pyrazole-4-carboxylic acid [2-(3-fluoro- 323
phenyl)-ethyl]-amide 715
1-(4-Fluoro-phenyl)-5-methyl-1H-pyrazole-4-carboxylic 353 acid
(benzo[1,3]dioxol-5-ylmethyl)-amide 716
1-Benzyl-1H-pyrazole-4-carboxylic acid 335
(benzo[1,3]dioxol-5-ylmethyl)-amide 717
1-(4-Fluoro-phenyl)-5-methyl-1H-pyrazole-4-carboxylic 341 acid
[2-(4-fluoro-phenyl)-ethyl]-amide 718
1-Benzyl-1H-pyrazole-4-carboxylic acid [2-(4-fluoro- 323
phenyl)-ethyl]-amide 719
1-(4-Fluoro-phenyl)-5-methyl-1H-pyrazole-4-carboxylic 343 acid
4-chloro-benzylamide 720 1-Benzyl-1H-pyrazole-4-carboxylic acid
4-chloro- 325 benzylamide 721
1-(4-Fluoro-phenyl)-5-methyl-1H-pyrazole-4-carboxylic 357 acid
[2-(3-chloro-phenyl)-ethyl]-amide 722
1-(4-Fluoro-phenyl)-5-methyl-1H-pyrazole-4-carboxylic 343 acid
2-chloro-benzylamide 723 1-Benzyl-1H-pyrazole-4-carboxylic acid
2-chloro- 325 benzylamide 724
1-(4-Fluoro-phenyl)-5-methyl-1H-pyrazole-4-carboxylic 357 acid
[2-(4-chloro-phenyl)-ethyl]-amide 725
1-Benzyl-1H-pyrazole-4-carboxylic acid [2-(4-chloro- 339
phenyl)-ethyl]-amide 726
1-(4-Fluoro-phenyl)-5-methyl-1H-pyrazole-4-carboxylic 327 acid
2-fluoro-benzylamide 727 1-Benzyl-1H-pyrazole-4-carboxylic acid
2-fluoro- 309 benzylamide 728
1-(4-Fluoro-phenyl)-5-methyl-1H-pyrazole-4-carboxylic 353 acid
[2-(2-methoxy-phenyl)-ethyl]-amide 729
1-Benzyl-1H-pyrazole-4-carboxylic acid [2-(2-methoxy- 335
phenyl)-ethyl]-amide 730
1-(4-Fluoro-phenyl)-5-methyl-1H-pyrazole-4-carboxylic 327 acid
4-fluoro-benzylamide 731 1-Benzyl-1H-pyrazole-4-carboxylic acid
4-fluoro- 309 benzylamide 732
1-(4-Fluoro-phenyl)-5-methyl-1H-pyrazole-4-carboxylic 353 acid
[2-(3-methoxy-phenyl)-ethyl]-amide 733
1-Benzyl-1H-pyrazole-4-carboxylic acid [2-(3-methoxy- 335
phenyl)-ethyl]-amide
734 1-(4-Fluoro-phenyl)-5-methyl-1H-pyrazole-4-carboxylic 310 acid
(pyridin-3-ylmethyl)-amide 735 1-Benzyl-1H-pyrazole-4-carboxylic
acid (pyridin-3- 292 ylmethyl)-amide 736
1-(4-Fluoro-phenyl)-5-methyl-1H-pyrazole-4-carboxylic 391 acid
[2-(3-trifluoromethyl-phenyl)-ethyl]-amide 737
1-Benzyl-1H-pyrazole-4-carboxylic acid [2-(3- 373
trifluoromethyl-phenyl)-ethyl]-amide 738
N-[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4- 395
yl]-3-methoxy-benzamide 739
N-[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4- 443
yl]-3-methanesulfonyl-benzamide 740
5-Methyl-1-phenyl-1H-pyrazole-4-carboxylic acid (3- 355
methanesulfonyl-phenyl)-amide 741
1-(4-Methoxy-phenyl)-5-methyl-1H-pyrazole-4- 385 carboxylic acid
(3-methanesulfonyl-phenyl)-amide 742
1-(4-Fluoro-phenyl)-5-methyl-1H-pyrazole-4-carboxylic 373 acid
(3-methanesulfonyl-phenyl)-amide 743
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 433 carboxylic
acid (5,6-dimethyl-1H-benzoimidazol-2-yl)- amide 744
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 419 carboxylic
acid (1-methyl-1H-benzoimidazol-2-yl)-amide 745
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 419 carboxylic
acid (1H-benzoimidazol-2-yl)-methyl-amide 746
5-Methyl-1-phenyl-1H-pyrazole-4-carboxylic acid (4-tert- 333
butyl-phenyl)-amide 747 5-Methyl-1-phenyl-1H-pyrazole-4-carboxylic
acid [2- 373 (2,4-dichloro-phenyl)-ethyl]-amide 748
5-Methyl-1-phenyl-1H-pyrazole-4-carboxylic acid (4- 333
phenyl-butyl)-amide 749 5-Methyl-1-phenyl-1H-pyrazole-4-carboxylic
acid [2- 333 (2,4-dimethyl-phenyl)-ethyl]-amide 750
5-Methyl-1-phenyl-1H-pyrazole-4-carboxylic acid [2-(2- 339
chloro-phenyl)-ethyl]-amide 751
5-Methyl-1-phenyl-1H-pyrazole-4-carboxylic acid (4- 319
isopropyl-phenyl)-amide 752
5-Methyl-1-phenyl-1H-pyrazole-4-carboxylic acid (2-o- 319
tolyl-ethyl)-amide 753 5-Methyl-1-phenyl-1H-pyrazole-4-carboxylic
acid [2-(4- 339 chloro-phenyl)-ethyl]-amide 754
1-(4-Methoxy-phenyl)-5-methyl-1H-pyrazole-4- 403 carboxylic acid
[2-(2,4-dichloro-phenyl)-ethyl]-amide 755
1-(4-Methoxy-phenyl)-5-methyl-1H-pyrazole-4- 363 carboxylic acid
(4-phenyl-butyl)-amide 756
1-(4-Methoxy-phenyl)-5-methyl-1H-pyrazole-4- 363 carboxylic acid
[2-(2,4-dimethyl-phenyl)-ethyl]-amide 757
1-(4-Methoxy-phenyl)-5-methyl-1H-pyrazole-4- 369 carboxylic acid
[2-(2-chloro-phenyl)-ethyl]-amide 758
1-(4-Methoxy-phenyl)-5-methyl-1H-pyrazole-4- 349 carboxylic acid
(4-isopropyl-phenyl)-amide 759
1-(4-Methoxy-phenyl)-5-methyl-1H-pyrazole-4- 349 carboxylic acid
(2-o-tolyl-ethyl)-amide 760
1-(4-Methoxy-phenyl)-5-methyl-1H-pyrazole-4- 369 carboxylic acid
[2-(4-chloro-phenyl)-ethyl]-amide 761
5-Methyl-1-phenyl-1H-pyrazole-4-carboxylic acid (2- 342
pyrrol-1-yl-phenyl)-amide 762
5-Methyl-1-phenyl-1H-pyrazole-4-carboxylic acid (2- 361
trifluoromethoxy-phenyl)-amide 763
5-Methyl-1-phenyl-1H-pyrazole-4-carboxylic acid 328
quinolin-8-ylamide 764 1-(4-Methoxy-phenyl)-5-methyl-1H-pyrazole-4-
363 carboxylic acid (4-tert-butyl-phenyl)-amide 765
1-(4-Methoxy-phenyl)-5-methyl-1H-pyrazole-4- 372 carboxylic acid
(2-pyrrol-1-yl-phenyl)-amide 766
1-(4-Methoxy-phenyl)-5-methyl-1H-pyrazole-4- 391 carboxylic acid
(2-trifluoromethoxy-phenyl)-amide 767
1-(4-Methoxy-phenyl)-5-methyl-1H-pyrazole-4- 358 carboxylic acid
quinolin-8-ylamide 768
N-[5-(4-Chloro-phenyl)-2-methyl-2H-pyrazol-3-yl]- 311 benzamide 769
N-(2-Methyl-5-thiophen-2-yl-2H-pyrazol-3-yl)-benzamide 283 770
N-(5-Cyclopropyl-2-methyl-2H-pyrazol-3-yl)-benzamide 241 771
N-(2-Methyl-5-phenyl-2H-pyrazol-3-yl)-benzamide 277 772
N-[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4- 365
yl]-benzamide 773
N-[5-(4-Chloro-phenyl)-2-methyl-2H-pyrazol-3-yl]-3- 329
fluoro-benzamide 774
N-(5-Cyclopropyl-2-methyl-2H-pyrazol-3-yl)-3-fluoro- 259 benzamide
775 N-[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4- 383
yl]-3-fluoro-benzamide 776
N-[5-(4-Chloro-phenyl)-2-methyl-2H-pyrazol-3-yl]-2- 341
methoxy-benzamide 777
2-Methoxy-N-(2-methyl-5-thiophen-2-yl-2H-pyrazol-3- 313
yl)-benzamide 778
N-(5-Cyclopropyl-2-methyl-2H-pyrazol-3-yl)-2-methoxy- 271 benzamide
779 2-Methoxy-N-(2-methyl-5-phenyl-2H-pyrazol-3-yl)- 307 benzamide
780 N-[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4- 395
yl]-2-methoxy-benzamide 781
N-[5-(4-Chloro-phenyl)-2-methyl-2H-pyrazol-3-yl]-3- 389
methanesulfonyl-benzamide 782
N-(5-Cyclopropyl-2-methyl-2H-pyrazol-3-yl)-3- 319
methanesulfonyl-benzamide 783
3-Methanesulfonyl-N-(2-methy-5-phenyl-2H-pyrazol-3- 355
yl)-benzamide 784
1-[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4- 458
yl]-3-(3-methanesulfonyl-phenyl)-urea 785
[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4-yl]- 411
carbamic acid 2-methoxy-phenyl ester 786
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 487 carboxylic
acid (1-methyl-5-trifluoromethyl-1H- benzoimidazol-2-yl)-amide 787
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 437 carboxylic
acid (5-fluoro-1-methyl-1H-benzoimidazol-2- yl)-amide 788
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 433 carboxylic
acid (1,6-dimethyl-1H-benzoimidzol-2-yl)- amide 789
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 487 carboxylic
acid (5,6-dichloro-1-methyl-1H- benzoimidazol-2-yl)-amide 792
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 475 carboxylic
acid [2-(2,4-dichloro-phenyl)-ethyl]-methyl- amide 793
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 414 carboxylic
acid (1-ethyl-pyrrolidin-2-ylmethyl)-methyl- amide 794
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 425 carboxylic
acid [2-(4-fluoro-phenyl)-ethyl]-methyl-amide 795
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 475 carboxylic
acid [2-(2,6-dichloro-phenyl)-ethyl]-methyl- amide 796
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 441 carboxylic
acid [2-(2-chloro-phenyl)-ethyl]-methyl-amide 797
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 425 carboxylic
acid [2-(2-fluoro-phenyl)-ethyl]-methyl-amide 798
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 425 carboxylic
acid [2-(3-fluoro-phenyl)-ethyl]-methyl-amide 799
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 441 carboxylic
acid [2-(3-chloro-phenyl)-ethyl]-methyl-amide 800
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 501 carboxylic
acid (5-ethanesulfonyl-2-methoxy-phenyl)- methyl-amide 801
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 441 carboxylic
acid [2-(4-chloro-phenyl)-ethyl]-methyl-amide 802
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 475 carboxylic
acid (2-fluoro-5-methanesulfonyl-phenyl)- methyl-amide 803
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 463 carboxylic
acid methyl-(3-trifluoromethoxy-phenyl)- amide 804
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 437 carboxylic
acid [2-(4-methoxy-phenyl)-ethyl]-methyl- amide 805
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 483 carboxylic
acid benzyl-(1-phenyl-ethyl)-amide 806
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 407 carboxylic
acid methyl-phenethyl-amide 807
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 471 carboxylic
acid bis-pyridin-3-ylmethyl-amide 808
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 471 carboxylic
acid bis-pyridin-2-ylmethyl-amide 809
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 433 carboxylic
acid (2-cyano-ethyl)-pyridin-3-ylmethyl-amide 810
[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4-yl]- 435
(4-pyridin-2-yl-piperazin-1-yl)-methanone 811
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 435 carboxylic
acid isopropyl-phenethyl-amide 812
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 483 carboxylic
acid benzyl-(1-phenyl-ethyl)-amide 813
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 408 carboxylic
acid ethyl-pyridin-4-ylmethy-amide 814
[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4-yl]- 341
(2,5-dihydro-pyrrol-1-yl)-methanone 815
[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4-yl]- 361
thiazolidin-3-yl-methanone 816
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 439 carboxylic
acid ethyl-(5-nitro-pyridin-2-yl)-amide 817
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 416 carboxylic
acid quinolin-6-ylamide 818
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 466 carboxylic
acid (4-nitro-benzyl)-propyl-amide 819
[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4-yl]- 446
[3-(4-methoxy-phenyl)-pyrazol-1-yl]-methanone 820
[1(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4-yl]- 426
(4-pyrrolidin-1-yl-piperidin-1-yl)-methanone 821
1-[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4- 414
yl]-3-(3-fluoro-phenyl)-thiourea 822
1-[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4- 432
yl]-3-(2,5-difluoro-phenyl)-thiourea 823
1-[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4- 448
yl]-3-(3,4-dichloro-phenyl)-urea 824
1-[1-(4-Chloro-cyclohexa-2,4-dienyl)-5-trifluoromethyl- 464
1H-pyrazol-4-yl]-3-(4-trifluoromethyl-phenyl)-thiourea 825
1-[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4- 464
yl]-3-(2,4-dichloro-phenyl)-thiourea 826
[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4-yl]- 411
carbamic acid 4-methoxy-phenyl ester 827
[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4-yl]- 381
carbamic acid phenyl ester 828
[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4-yl]- 361
carbamic acid isobutyl ester 829
1-[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4- 464
yl]-3-(2,6-diisopropyl-phenyl)-urea 830
[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4-yl]- 347
carbamic acid propyl ester 832
1-Pyridin-2-yl-5-trifluoromethyl-1H-pyrazole-4- 410 carboxylic acid
(3-methanesulfonyl-phenyl)-amide 833
5-Trifluoromethyl-1-(5-trifluoromethyl-pyridin-2-yl)-1H- 482
pyrazole-4-carboxylic acid 4-trifluoromethyl-benzylamide 834
5-Trifluoromethyl-1-(5-trifluoromethyl-pyridin-2-yl)-1H- 446
pyrazole-4-carboxylic acid [2-(2-fluoro-phenyl)-ethyl]- amide 835
5-Trifluoromethyl-1-(5-trifluoromethyl-pyridin-2-yl)-1H- 440
pyrazole-4-carboxylic acid (1H-benzoimidazol-2-yl)- amide 836
5-Trifluoromethyl-1-(5-trifluoromethyl-pyridin-2-yl)-1H- 401
pyrazole-4-carboxylic acid pyridin-4-ylamide 837
5-Trifluoromethyl-1-(5-trifluoromethyl-pyridin-2-yl)-1H- 478
pyrazole-4-carboxylic acid (3-methanesulfonyl-phenyl)- amide 838
1-(6-Chloro-pyridin-2-yl)-5-trifluoromethyl-1H-pyrazole- 448
4-carboxylic acid 4-trifluoromethyl-benzylamide 839
1-(6-Chloro-pyridin-2-yl)-5-trifluoromethyl-1H-pyrazole- 412
4-carboxylic acid [2-(2-fluoro-phenyl)-ethyl]-amide 840
1-(6-Chloro-pyridin-2-yl)-5-trifluoromethyl-1H-pyrazole- 406
4-carboxylic acid (1H-benzoimidazol-2-yl)-amide 841
1-(6-Chloro-pyridin-2-yl)-5-trifluoromethyl-1H-pyrazole- 367
4-carboxylic acid pyridin-4-ylamide 842
1-(6-Chloro-pyridin-2-yl)-5-trifluoromethyl-1H-pyrazole- 444
4-carboxylic acid (3-methanesulfonyl-phenyl)-amide 843
1-(6-Hydroxy-pyridazin-3-yl)-5-trifluoromethyl-1H- 427
pyrazole-4-carboxylic acid (3-methanesulfonyl-phenyl)- amide 844
1-(6-Hydroxy-pyridazin-3-yl)-5-trifluoromethyl-1H- 389
pyrazole-4-carboxylic acid (1H-benzoimidazol-2-yl)- amide 845
1-(6-Hydroxy-pyridazin-3-yl)-5-trifluoromethyl-1H- 395
pyrazole-4-carboxylic acid [2-(2-fluoro-phenyl)-ethyl]- amide 846
1-(6-Hydroxy-pyridazin-3-yl)-5-trifluoromethyl-1H- 431
pyrazole-4-carboxylic acid 4-trifluoromethyl-benzylamide 847
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 408 carboxylic
acid methyl-(2-pyridin-2-yl-ethyl)-amide 848
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 394 carboxylic
acid methyl-pyridin-3-ylmethyl-amide 849
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 416 carboxylic
acid quinolin-3-ylamide 850
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 533 carboxylic
acid benzyl-(3-methanesulfonyl-phenyl)-amide 851
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 471 carboxylic
acid ethyl-(3-methanesulfonyl-phenyl)-amide 852
[[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 529
carbonyl]-(3-methanesulfonyl-phenyl)-amino]-acetic acid ethyl ester
853 1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 482
carboxylic acid cyanomethyl-(3-methanesulfonyl-phenyl)- amide
854 1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 583
carboxylic acid (3-methanesulfonyl-phenyl)-naphthalen-2-
ylmethyl-amide 855
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 534 carboxylic
acid (3-methanesulfonyl-phenyl)-pyridin-3- ylmethyl-amide 856
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 534 carboxylic
acid (3-methanesulfonyl-phenyl)-pyridin-2- ylmethyl-amide 857
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 567 carboxylic
acid (4-chloro-benzyl)-(3-methanesulfonyl- phenyl)-amide 858
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 534 carboxylic
acid (3-methanesulfonyl-phenyl)-pyridin-4- ylmethyl-amide 859
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 483 carboxylic
acid allyl-(3-methanesulfonyl-phenyl)-amide 860
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 552 carboxylic
acid (3,5-dimethyl-isoxazol-4-ylmethyl)-(3- 552
methanesulfonyl-phenyl)-amide 861
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 551 carboxylic
acid benzyl-[2-(2,6-dichloro-phenyl)-ethyl]- amide 862
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 601 carboxylic
acid [2-(2,6-dichloro-phenyl)-ethyl]- naphthalen-2-ylmethyl-amide
863 1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 552
carboxylic acid [2-(2,6-dichloro-phenyl)-ethyl]-pyridin-3-
ylmethyl-amide 864
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 552 carboxylic
acid [2-(2,6-dichloro-phenyl)-ethyl]-pyridin-2- 552 ylmethyl-amide
865 1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 585
carboxylic acid (4-chloro-benzyl)-[2-(2,6-dichloro-
phenyl)-ethyl]-amide 866
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 552 carboxylic
acid [2-(2,6-dichloro-phenyl)-ethyl]-pyridin-4- ylmethyl-amide 867
1-Benzyl-3-[1-(4-chloro-phenyl)-5-trifluoromethyl-1H- 394
pyrazol-4-yl]-urea 868
1-[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4- 408
yl]-3-phenethyl-urea 869
1-[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4- 426
yl]-3-[2-(4-fluoro-phenyl)-ethyl]-urea 870 Morpholine-4-carboxylic
acid [1-(4-chloro-phenyl)-5- 374
trifluoromethyl-1H-pyrazol-4-yl]-amide 871
1-Butyl-3-[1-(4-chloro-phenyl)-5-trifluoromethyl-1H- 360
pyrazol-4-yl]-urea 872
1-[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4- 422
yl]-3-(2-m-tolyl-ethyl)-urea 873
1-[2-(4-Chloro-phenyl)-ethyl]-3-[1-(4-chloro-phenyl)-5- 442
trifluoromethyl-1H-pyrazol-4-yl]-urea 874
1-[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4- 422
yl]-3-(3-phenyl-propyl)-urea 875
1-[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4- 372
yl]-3-cyclopentyl-urea 876
1-Benzo[1,3]dioxol-5-ylmethyl-3-[1-(4-chloro-phenyl)-5- 438
trifluoromethyl-1H-pyrazol-4-yl]-urea 877
3-[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4- 409
yl]-1-methyl-1-pyridin-3-ylmethyl-urea 878
3-[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4- 423
yl]-1-methyl-1-(2-pyridin-2-yl-ethyl)-urea 879
1-Pyridin-2-yl-5-trifluoromethyl-1H-pyrazole-4- 414 carboxylic acid
3-trifluoromethyl-benzylamide 880
1-Pyridin-2-yl-5-trifluoromethyl-1H-pyrazole-4- 378 carboxylic acid
[2-(2-fluoro-phenyl)-ethyl]-amide 881
1-Pyridin-2-yl-5-trifluoromethyl-1H-pyrazole-4- 372 carboxylic acid
(1H-benzoimidazol-2-yl)-amide 882
1-Pyridin-2-yl-5-trifluoromethyl-1H-pyrazole-4- 333 carboxylic acid
pyridin-4-ylamide 883
1-Pyridin-2-yl-5-trifluoromethyl-1H-pyrazole-4- 428 carboxylic acid
[2-(2,6-dichloro-phenyl)-ethyl]-amide 884
1-(3-Chloro-phenyl)-3-[1-(4-chloro-phenyl)-5- 414
trifluoromethyl-1H-pyrazol-4-yl]-urea 885
1-[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4- 448
yl]-3-(4-trifluoromethyl-phenyl)-urea 886
1-[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4- 371
yl]-3-isoxazol-3-yl-urea 887
1-(2-tert-Butyl-phenyl)-3-[1-(4-chloro-phenyl)-5- 436
trifluoromethyl-1H-pyrazol-4-yl]-urea 888
1-[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4- 380
yl]-3-phenyl-urea 889
1-[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4- 445
yl]-3-(2-pyrrol-1-yl-phenyl)-urea 890
3-(2-Chloro-phenyl)-5-methyl-isoxazole-4-carboxylic acid 480
[1-(4-chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4-yl]- amide 891
1,3-Bis-[1-(4-chloro-phenyl)-5-trifluoromethyl-1H- 548
pyrazol-4-yl]-urea 892 4-Acetyl-[1,4]diazepane-1-carboxylic acid
[1-(4-chloro- 429 phenyl)-5-trifluoromethyl-1H-pyrazol-4-yl]-amide
893 1-Allyl-3-[1-(4-chloro-phenyl)-5-trifluoromethyl-1H- 344
pyrazol-4-yl]-urea 894 1-(2-Amino-benzyl)-3-[1-(4-chloro-phenyl)-5-
409 trifluoromethyl-1H-pyrazol-4-yl]-urea 895
1-[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4- 445
yl]-3-(4-diethylamino-1-methyl-butyl)-urea 896
1-[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4- 392
yl]-3-[2-(2-hydroxy-ethoxy)-ethyl]-urea 897
1-[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4- 465
yl]-3-[2-(ethyl-m-tolyl-amino)-ethyl]-urea 898
1-[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4- 415
yl]-3-[2-(1-methyl-pyrrolidin-2-yl)-ethyl]-urea 899
1-[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4- 417
yl]-3-(2-morpholin-4-yl-ethyl)-urea 900
1-[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4- 415
yl]-3-(2-piperidin-1-yl-ethyl)-urea 901
1-[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4- 409
yl]-3-(2-pyridin-2-yl-ethyl)-urea 902
1-[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4- 401
yl]-3-(2-pyrrolidin-1-yl-ethyl)-urea 903
1-[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4- 420
yl]-3-(1H-indazol-6-yl)-urea 904
1-[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4- 395
yl]-3-pyridin-3-ylmethyl-urea 905
1-[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4- 395
yl]-3-pyridin-4-ylmethyl-urea 906
1-[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4- 424
yl]-3-(2-hydroxy-2-phenyl-ethyl)-urea 907
1-[2-(4-Amino-phenyl)-ethyl]-3-[1-(4-chloro-phenyl)-5- 423
trifluoromethyl-1H-pyrazol-4-yl]-urea 908
1-[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4- 446
yl]-3-(5-phenyl-2H-pyrazol-3-yl)-urea 909
(3-{3-[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol- 461
4-yl]-ureido}-propyl)-carbamic acid tert-butyl ester 910
1-[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4- 412
yl]-3-(3-imidazol-1-yl-propyl)-urea 911
1-(1-Benzyl-pyrrolidin-3-yl)-3-[1-(4-chloro-phenyl)-5- 463
trifluoromethyl-1H-pyrazol-4-yl]-urea 912
4-Benzyl-piperazine-1-carboxylic acid [1-(4-chloro- 463
phenyl)-5-trifluoromethyl-1H-pyrazol-4-yl]-amide 913
4-(2-Chloro-phenyl)-piperazine-1-carboxylic acid [1-(4- 483
chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4-yl]-amide 914
3-[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4- 392
yl]-1,1-bis-(2-hydroxy-ethyl)-urea 915
1-[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4- 403
yl]-3-(2-diethylamino-ethyl)-urea 916
1-[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4- 417
yl]-3-(3-diethylamino-propyl)-urea 917
1-[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4- 454
yl]-3-(2,3-dimethoxy-benzyl)-urea 918
1-[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4- 454
yl]-3-(2,4-dimethoxy-benzyl)-urea 919
2,6-Dimethyl-morpholine-4-carboxylic acid [1-(4-chloro- 402
phenyl)-5-trifluoromethyl-1H-pyrazol-4-yl]-amide 920
3-[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4- 486
yl]-1,1-bis-pyridin-2-ylmethyl-urea 921
3-[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4- 486
yl]-1,1-bis-pyridin-3-ylmethyl-urea 922
3-[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4- 376
yl]-1-ethyl-1-(2-hydroxy-ethyl)-urea 923
3-[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4- 423
yl]-1-ethyl-1-pyridin-4-ylmethyl-urea 924
v4-(2-Hydroxy-ethyl)-piperazine-1-carboxylic acid [1-(4- 417
chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4-yl]-amide 925
4-Methyl-[1,4]diazepane-1-carboxylic acid [1-(4-chloro- 401
phenyl)-5-trifluoromethyl-1H-pyrazol-4-yl]-amide 926
3-[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4- 415
yl]-1-methyl-1-(1-methyl-piperidin-4-yl)-urea 927
4-Methyl-piperazine-1-carboxylic acid [1-(4-chloro- 387
phenyl)-5-trifluoromethyl-1H-pyrazol-4-yl]-amide 928
1-[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4- 378
yl]-3-(2-methylsulfanyl-ethyl)-urea 929
4-Pyrimidin-2-yl-piperazine-1-carboxylic acid [1-(4- 451
chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4-yl]-amide 930
4-Benzo[1,3]dioxol-5-ylmethyl-piperazine-1-carboxylic 507 acid
[1-(4-chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4- yl]-amide 931
3-[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4- 448
yl]-1-(2-cyano-ethyl)-1-pyridin-3-ylmethyl-urea 932
3-Hydroxy-pyrrolidine-1-carboxylic acid [1-(4-chloro- 374
phenyl)-5-trifluoromethyl-1H-pyrazol-4-yl]-amide 933
4-Pyrrolidin-1-yl-piperidine-1-carboxylic acid [1-(4- 441
chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4-yl]-amide 934
1-[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4- 388
yl]-3-(tetrahydro-furan-2-ylmethyl)-urea 935
Thiazolidine-3-carboxylic acid [1-(4-chloro-phenyl)-5- 376
trifluoromethyl-1H-pyrazol-4-yl]-amide 936
Thiomorpholine-4-carboxylic acid [1-(4-chloro-phenyl)-5- 390
trifluoromethyl-1H-pyrazol-4-yl]-amide 937
1-[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4- 414
yl]-3-(2-thiophen-2-yl-ethyl)-urea 938
1-[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4- 400
yl]-3-thiophen-2-ylmethyl-urea 939
5-Methyl-1-phenyl-1H-pyrazole-4-carboxylic acid [1-(4- 430
trifluoromethoxy-phenyl)-pyrrolidin-3-yl]-amide 940
5-Methyl-1-phenyl-1H-pyrazole-4-carboxylic acid [1-(4- 430
trifluoromethoxy-phenyl)-pyrrolidin-3-yl]-amide 941
5-Methyl-1-phenyl-1H-pyrazole-4-carboxylic acid [1-(3- 430
trifluoromethoxy-phenyl)-pyrrolidin-3-yl]-amide 942
5-Methyl-1-phenyl-1H-pyrazole-4-carboxylic acid [1-(3- 430
trifluoromethoxy-phenyl)-pyrrolidin-3-yl]-amide 943
5-Methyl-1-phenyl-1H-pyrazole-4-carboxylic acid [1-(3- 414
trifluoromethyl-phenyl)-pyrrolidin-3-yl]-amide 944
5-Methyl-1-phenyl-1H-pyrazole-4-carboxylic acid [1-(3- 414
trifluoromethyl-phenyl)-pyrrolidin-3-yl]-amide 945
1-(6-Chloro-pyridin-2-yl)-5-trifluoromethyl-1H-pyrazole- 440
4-carboxylic acid 2,4-dimethoxy-benzylamide 946
1-(6-Chloro-pyridin-2-yl)-5-trifluoromethyl-1H-pyrazole- 424
4-carboxylic acid (benzo[1,3]dioxol-5-ylmethyl)-amide 947
1-(6-Chloro-pyridin-2-yl)-5-trifluoromethyl-1H-pyrazole- 384
4-carboxylic acid (3-fluoro-phenyl)-amide 948
[1-(6-Chloro-pyridin-2-yl)-5-trifluoromethyl-1H-pyrazol- 406
4-yl]-(3,4-dihydro-2H-quinolin-1-yl)-methanone 949
1-(6-Chloro-pyridin-2-yl)-5-trifluoromethyl-1H-pyrazole- 396
4-carboxylic acid (3-methoxy-phenyl)-amide 950
1-(6-Chloro-pyridin-2-yl)-5-trifluoromethyl-1H-pyrazole- 406
4-carboxylic acid (2-isopropenyl-phenyl)-amide 951
1-(6-Chloro-pyridin-2-yl)-5-trifluoromethyl-1H-pyrazole- 381
4-carboxylic acid (pyridin-3-ylmethyl)-amide 952
1-(6-Chloro-pyridin-2-yl)-5-trifluoromethyl-1H-pyrazole- 462
4-carboxylic acid [2-(2,6-dichloro-phenyl)-ethyl]-amide 953
1-(6-Chloro-pyridin-2-yl)-5-trifluoromethyl-1H-pyrazole- 451
4-carboxylic acid [2-(ethyl-m-tolyl-amino)-ethyl]-amide 954
[4-(2-Chloro-phenyl)-piperazin-1-yl]-[1-(6-chloro- 469
pyridin-2-yl)-5-trifluoromethyl-1H-pyrazol-4-yl]- methanone 955
1-(6-Chloro-pyridin-2-yl)-5-trifluoromethyl-1H-pyrazole- 449
4-carboxylic acid (1-benzyl-pyrrolidin-3-yl)-amide 956
(4-Benzyl-piperazin-1-yl)-[1-(6-chloro-pyridin-2-yl)-5- 449
trifluoromethyl-1H-pyrazol-4-yl]-methanone 957
1-Pyrimidin-2-yl-5-trifluoromethyl-1H-pyrazole-4- 407 carboxylic
acid 2,4-dimethoxy-benzylamide 958
1-Pyrimidin-2-yl-5-trifluoromethyl-1H-pyrazole-4- 391 carboxylic
acid (benzo[1,3]dioxol-5-ylmethyl)-amide 959
1-Pyrimidin-2-yl-5-trifluoromethyl-1H-pyrazole-4- 351 carboxylic
acid (3-fluoro-phenyl)-amide 960
(3,4-Dihydro-2H-quinolin-1-yl)-(1-pyrimidin-2-yl-5- 373
trifluoromethyl-1H-pyrazol-4-yl)-methanone 961
1-Pyrimidin-2-yl-5-trifluoromethyl-1H-pyrazole-4- 363 carboxylic
acid (3-methoxy-phenyl)-amide 962
1-Pyrimidin-2-yl-5-trifluoromethyl-1H-pyrazole-4- 373 carboxylic
acid (2-isopropenyl-phenyl)-amide 963
1-Pyrimidin-2-yl-5-trifluoromethyl-1H-pyrazole-4- 348 carboxylic
acid (pyridin-3-ylmethyl)-amide 964
1-Pyrimidin-2-yl-5-trifluoromethyl-1H-pyrazole-4- 429 carboxylic
acid [2-(2,6-dichloro-phenyl)-ethyl]-amide 965
1-Pyrimidin-2-yl-5-trifluoromethyl-1H-pyrazole-4- 418 carboxylic
acid [2-(ethyl-m-tolyl-amino)-ethyl]-amide 966
[4-(2-Chloro-phenyl)-piperazin-1-yl]-(1-pyrimidin-2-yl-5- 436
trifluoromethyl-1H-pyrazol-4-yl)-methanone 967
1-Pyrimidin-2-yl-5-trifluoromethyl-1H-pyrazole-4- 416 carboxylic
acid (1-benzyl-pyrrolidin-3-yl)-amide 968
(4-Benzyl-piperazin-1-yl)-(1-pyrimidin-2-yl-5- 416
trifluoromethyl-1H-pyrazol-4-yl)-methanone 969
1-(4-Trifluoromethoxy-phenyl)-5-trifluoromethyl-1H- 489
pyrazole-4-carboxylic acid 2,4-dimethoxy-benzylamide 970
1-(4-Trifluoromethoxy-phenyl)-5-trifluoromethyl-1H- 473
pyrazole-4-carboxylic acid (benzo[1,3]dioxol-5- ylmethyl)-amide 971
1-(4-Trifluoromethoxy-phenyl)-5-trifluoromethyl-1H- 433
pyrazole-4-carboxylic acid (3-fluoro-phenyl)-amide 972
(3,4-Dihydro-2H-quinolin-1-yl)-[1-(4-trifluoromethoxy- 455
phenyl)-5-trifluoromethyl-1H-pyrazol-4-yl]-methanone 973
1-(4-Trifluoromethoxy-phenyl)-5-trifluoromethyl-1H- 445
pyrazole-4-carboxylic acid (3-methoxy-phenyl)-amide 974
1-(4-Trifluoromethoxy-phenyl)-5-trifluoromethyl-1H- 455
pyrazole-4-carboxylic acid (2-isopropenyl-phenyl)-amide 975
1-(4-Trifluoromethoxy-phenyl)-5-trifluoromethyl-1H- 430
pyrazole-4-carboxylic acid (pyridin-3-ylmethyl)-amide 976
1-(4-Trifluoromethoxy-phenyl)-5-trifluoromethyl-1H- 511
pyrazole-4-carboxylic acid [2-(2,6-dichloro-phenyl)- ethyl]-amide
977 1-(4-Trifluoromethoxy-phenyl)-5-trifluoromethyl-1H- 500
pyrazole-4-carboxylic acid [2-(ethyl-m-tolyl-amino)- ethyl]-amide
978 [4-(2-Chloro-phenyl)-piperazin-1-yl]-[1-(4- 518
trifluoromethoxy-phenyl)-5-trifluoromethyl-1H-pyrazol-4-
yl]-methanone 979
1-(4-Trifluoromethoxy-phenyl)-5-trifluoromethyl-1H- 498
pyrazole-4-carboxylic acid (1-benzyl-pyrrolidin-3-yl)- amide 980
(4-Benzyl-piperazin-1-yl)-[1-(4-trifluoromethoxy-phenyl)- 498
5-trifluoromethyl-1H-pyrazol-4-yl]-methanone 981
1-Pyridin-2-yl-5-trifluoromethyl-1H-pyrazole-4- 406 carboxylic acid
2,4-dimethoxy-benzylamide 982
1-Pyridin-2-yl-5-trifluoromethyl-1H-pyrazole-4- 390 carboxylic acid
(benzo[1,3]dioxol-5-ylmethyl)-amide 983
1-Pyridin-2-yl-5-trifluoromethyl-1H-pyrazole-4- 350 carboxylic acid
(3-fluoro-phenyl)-amide 984
(3,4-Dihydro-2H-quinolin-1-yl)-(1-pyridin-2-yl-5- 372
trifluoromethyl-1H-pyrazol-4-yl)-methanone 985
1-Pyridin-2-yl-5-trifluoromethyl-1H-pyrazole-4- 362 carboxylic acid
(3-methoxy-phenyl)-amide 986
1-Pyridin-2-yl-5-trifluoromethyl-1H-pyrazole-4- 372 carboxylic acid
(2-isopropenyl-phenyl)-amide 987
1-Pyridin-2-yl-5-trifluoromethyl-1H-pyrazole-4- 347 carboxylic acid
(pyridin-3-ylmethyl)-amide 988
1-Pyridin-2-yl-5-trifluoromethyl-1H-pyrazole-4- 417 carboxylic acid
[2-(ethyl-m-tolyl-amino)-ethyl]-amide 989
[4-(2-Chloro-phenyl)-piperazin-1-yl]-(1-pyridin-2-yl-5- 435
trifluoromethyl-1H-pyrazol-4-yl)-methanone 990
1-Pyridin-2-yl-5-trifluoromethyl-1H-pyrazole-4- 415 carboxylic acid
(1-benzyl-pyrrolidin-3-yl)-amide 991
(4-Benzyl-piperazin-1-yl)-(1-pyridin-2-yl-5- 415
trifluoromethyl-1H-pyrazol-4-yl)-methanone 992
1-(6-Chloro-pyridin-2-yl)-5-trifluoromethyl-1H-pyrazole- 450
4-carboxylic acid (2-trifluoromethoxy-phenyl)-amide 993
1-(6-Chloro-pyridin-2-yl)-5-trifluoromethyl-1H-pyrazole- 422
4-carboxylic acid (4-tert-butyl-phenyl)-amide 994
1-(6-Chloro-pyridin-2-yl)-5-trifluoromethyl-1H-pyrazole- 472
4-carboxylic acid bis-pyridin-2-ylmethyl-amide 995
1-(6-Chloro-pyridin-2-yl)-5-trifluoromethyl-1H-pyrazole- 428
4-carboxylic acid [2-(4-chloro-phenyl)-ethyl]-amide 996
1-(6-Chloro-pyridin-2-yl)-5-trifluoromethyl-1H-pyrazole- 412
4-carboxylic acid [2-(4-fluoro-phenyl)-ethyl]-amide 997
1-(6-Chloro-pyridin-2-yl)-5-trifluoromethyl-1H-pyrazole- 398
4-carboxylic acid (4-fluoro-phenyl)-methyl-amide 998
4-{[1-(6-Chloro-pyridin-2-yl)-5-trifluoromethyl-1H- 438
pyrazole-4-carbonyl]-amino}-benzoic acid ethyl ester 999
1-(6-Chloro-pyridin-2-yl)-5-trifluoromethyl-1H-pyrazole- 431
4-carboxylic acid (2-pyrrol-1-yl-phenyl)-amide 1000
1-(6-Chloro-pyridin-2-yl)-5-trifluoromethyl-1H-pyrazole- 401
4-carboxylic acid (5-chloro-pyridin-2-yl)-amide 1001
1-(6-Chloro-pyridin-2-yl)-5-trifluoromethyl-1H-pyrazole- 417
4-carboxylic acid isoquinolin-1-ylamide 1002
1-Pyrimidin-2-yl-5-trifluoromethyl-1H-pyrazole-4- 417 carboxylic
acid (2-trifluoromethoxy-phenyl)-amide 1003
1-Pyrimidin-2-yl-5-trifluoromethyl-1H-pyrazole-4- 389 carboxylic
acid (4-tert-butyl-phenyl)-amide 1004
1-Pyrimidin-2-yl-5-trifluoromethyl-1H-pyrazole-4- 439 carboxylic
acid bis-pyridin-2-ylmethyl-amide 1005
1-Pyrimidin-2-yl-5-trifluoromethyl-1H-pyrazole-4- 395 carboxylic
acid [2-(4-chloro-phenyl)-ethyl]-amide 1006
1-Pyrimidin-2-yl-5-trifluoromethyl-1H-pyrazole-4- 379 carboxylic
acid [2-(4-fluoro-phenyl)-ethyl]-amide 1007
1-Pyrimidin-2-yl-5-trifluoromethyl-1H-pyrazole-4- 365 carboxylic
acid (4-fluoro-phenyl)-methyl-amide 1008
1-Pyrimidin-2-yl-5-trifluoromethyl-1H-pyrazole-4- 411 carboxylic
acid (3-methanesulfonyl-phenyl)-amide 1009
4-[(1-Pyrimidin-2-yl-5-trifluoromethyl-1H-pyrazole-4- 405
carbonyl)-amino]-benzoic acid ethyl ester 1010
1-Pyrimidin-2-yl-5-trifluoromethyl-1H-pyrazole-4- 398 carboxylic
acid (2-pyrrol-1-yl-phenyl)-amide 1011
1-Pyrimidin-2-yl-5-trifluoromethyl-1H-pyrazole-4- 368 carboxylic
acid (5-chloro-pyridin-2-yl)-amide 1012
1-Pyrimidin-2-yl-5-trifluoromethyl-1H-pyrazole-4- 384 carboxylic
acid isoquinolin-1-ylamide 1013
1-(4-Trifluoromethoxy-phenyl)-5-trifluoromethyl-1H- 499
pyrazole-4-carboxylic acid (2-trifluoromethoxy-phenyl)- amide 1014
1-(4-Trifluoromethoxy-phenyl)-5-trifluoromethyl-1H- 471
pyrazole-4-carboxylic acid (4-tert-butyl-phenyl)-amide 1015
1-(4-Trifluoromethoxy-phenyl)-5-trifluoromethyl-1H- 521
pyrazole-4-carboxylic acid bis-pyridin-2-ylmethyl-amide 1016
1-(4-Trifluoromethoxy-phenyl)-5-trifluoromethyl-1H- 477
pyrazole-4-carboxylic acid [2-(4-chloro-phenyl)-ethyl]- amide 1017
1-(4-Trifluoromethoxy-phenyl)-5-trifluoromethyl-1H- 461
pyrazole-4-carboxylic acid [2-(4-fluoro-phenyl)-ethyl]- amide 1018
1-(4-Trifluoromethoxy-phenyl)-5-trifluoromethyl-1H- 447
pyrazole-4-carboxylic acid (4-fluoro-phenyl)-methyl- amide 1019
1-(4-Trifluoromethoxy-phenyl)-5-trifluoromethyl-1H- 493
pyrazole-4-carboxylic acid (3-methanesulfonyl-phenyl)- amide 1020
4-{[1-(4-Trifluoromethoxy-phenyl)-5-trifluoromethyl-1H- 487
pyrazole-4-carbonyl]-amino}-benzoic acid ethyl ester 1021
1-(4-Trifluoromethoxy-phenyl)-5-trifluoromethyl-1H- 480
pyrazole-4-carboxylic acid (2-pyrrol-1-yl-phenyl)-amide 1022
1-(4-Trifluoromethoxy-phenyl)-5-trifluoromethyl-1H- 450
pyrazole-4-carboxylic acid (5-chloro-pyridin-2-yl)-amide 1023
1-(4-Trifluoromethoxy-phenyl)-5-trifluoromethyl-1H- 466
pyrazole-4-carboxylic acid isoquinolin-1-ylamide 1024
1-Pyridin-2-yl-5-trifluoromethyl-1H-pyrazole-4- 416 carboxylic acid
(2-trifluoromethoxy-phenyl)-amide 1025
1-Pyridin-2-yl-5-trifluoromethyl-1H-pyrazole-4- 388 carboxylic acid
(4-tert-butyl-phenyl)-amide 1026
1-Pyridin-2-yl-5-trifluoromethyl-1H-pyrazole-4- 438 carboxylic acid
bis-pyridin-2-ylmethyl-amide 1027
1-Pyridin-2-yl-5-trifluoromethyl-1H-pyrazole-4- 394 carboxylic acid
[2-(4-chloro-phenyl)-ethyl]-amide 1028
1-Pyridin-2-yl-5-trifluoromethyl-1H-pyrazole-4- 378 carboxylic acid
[2-(4-fluoro-phenyl)-ethyl]-amide 1029
1-Pyridin-2-yl-5-trifluoromethyl-1H-pyrazole-4- 364 carboxylic acid
(4-fluoro-phenyl)-methyl-amide 1030
4-[(1-Pyridin-2-yl-5-trifluoromethyl-1H-pyrazole-4- 404
carbonyl)-amino]-benzoic acid ethyl ester 1031
1-Pyridin-2-yl-5-trifluoromethyl-1H-pyrazole-4- 397 carboxylic acid
(2-pyrrol-1-yl-phenyl)-amide 1032
1-Pyridin-2-yl-5-trifluoromethyl-1H-pyrazole-4- 367 carboxylic acid
(5-chloro-pyridin-2-yl)-amide 1033
1-Pyridin-2-yl-5-trifluoromethyl-1H-pyrazole-4- 383 carboxylic acid
isoquinolin-1-ylamide 1034
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 450 carboxylic
acid [2-(ethyl-m-tolyl-amino)-ethyl]-amide 1035
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 448 carboxylic
acid (1-benzyl-pyrrolidin-3-yl)-amide 1036
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 448 carboxylic
acid (1-benzyl-pyrrolidin-3-yl)-amide 1037
1-(1-Benzyl-pyrrolidin-3-yl)-3-[1-(4-chloro-phenyl)-5- 463
trifluoromethyl-1H-pyrazol-4-yl]-urea 1038
1-(1-Benzyl-pyrrolidin-3-yl)-3-[1-(4-chloro-phenyl)-5- 463
trifluoromethyl-1H-pyrazol-4-yl]-urea 1039
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 462 carboxylic
acid (1-benzyl-piperidin-4-yl)-amide 1040
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 372 carboxylic
acid piperidin-4-ylamide 1041
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 451 carboxylic
acid (1-sulfamoyl-piperidin-4-yl)-amide 1042
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 479 carboxylic
acid (1-dimethylsulfamoyl-piperidin-4-yl)- amide 1044
4-{[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole- 444
4-carbonyl]-amino}-piperidine-1-carboxylic acid ethyl ester 1045
{1-[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole- 472
4-carbonyl]-piperidin-4-yl}-carbamic acid tert-butyl ester 1046
(4-Amino-piperidin-1-yl)-[1-(4-chloro-phenyl)-5- 372
trifluoromethyl-1H-pyrazol-4-yl]-methanone 1049
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 399 carboxylic
acid (3-chloro-phenyl)-amide 1050
3-{[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole- 437
4-carbonyl]-amino}-benzoic acid ethyl ester 1052
3-{[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole- 409
4-carbonyl]-amino}-benzoic acid 1053
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 460 carboxylic
acid [3-(3,5-dimethyl-isoxazol-4-yl)-phenyl]- amide 1054
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 444 carboxylic
acid (3-sulfamoyl-phenyl)-amide 1055
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 472 carboxylic
acid (3-dimethylsulfamoyl-phenyl)-amide 1056
(4-Benzylamino-piperidin-1-yl)-[1-(4-chloro-phenyl)-5- 462
trifluoromethyl-1H-pyrazol-4-yl]-methanone 1057
[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4-yl]- 480
[4-(4-fluoro-benzylamino)-piperidin-1-yl]-methanone 1058
[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4-yl]- 492
[4-(4-methoxy-benzylamino)-piperidin-1-yl]-methanone 1059
[4-(4-Chloro-benzylamino)-piperidin-1-yl]-[1-(4-chloro- 496
phenyl)-5-trifluoromethyl-1H-pyrazol-4-yl]-methanone 1060
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 480 carboxylic
acid [1-(4-fluoro-benzyl)-piperidin-4-yl]-amide 1061
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 496 carboxylic
acid [1-(3-chloro-benzyl)-piperidin-4-yl]- amide 1062
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 480 carboxylic
acid [1-(2-fluoro-benzyl)-piperidin-4-yl]-amide 1063
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 546 carboxylic
acid [1-(4-trifluoromethoxy-benzyl)-piperidin- 4-yl]-amide 1064
1-[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 554
carbonyl]-piperidine-2-carboxylic acid (3-
methanesulfonyl-phenyl)-amide 1065
[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4-yl]- 373
(4-hydroxy-piperidin-1-yl)-methanone 1066
[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4-yl]- 491
[2-(5-fluoro-1H-benzoimidazol-2-yl)-piperidin-1-yl]- methanone 1067
[2-(1H-Benzoimidazol-2-yl)-piperidin-1-yl]-[1-(4-chloro- 473
phenyl)-5-trifluoromethyl-1H-pyrazol-4-yl]-methanone 1068
1-(3-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 427 carboxylic
acid (3-methanesulfonyl-phenyl)-amide 1069
1-(3,4-Difluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 445
carboxylic acid (3-methanesulfonyl-phenyl)-amide 1070
1-(3-Fluoro-phenyl)-5-tifluoromethyl-1H-pyrazole-4- 377 carboxylic
acid phenethyl-amide 1071
1-(3,4-Difluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 395
carboxylic acid phenethyl-amide 1072
1-(3-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 377 carboxylic
acid benzyl-methyl-amide 1073
1-(3,4-Difluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 395
carboxylic acid benzyl-methyl-amide 1074
1-(3-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 431 carboxylic
acid 3-trifluoromethyl-benzylamide 1075
1-(3,4-Difluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 449
carboxylic acid 3-trifluoromethyl-benzylamide 1076
1-[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 504
carbonyl]-piperidine-2-carboxylic acid phenethyl-amide 1077
1-[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 504
carbonyl]-piperidine-2-carboxylic acid benzyl-methyl- amide 1078
1-[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 558
carbonyl]-piperidine-2-carboxylic acid 3-trifluoromethyl-
benzylamide 1079
1-(3-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 446 carboxylic
acid (1-benzyl-pyrrolidin-3-yl)-methyl-amide 1080
1-(3,4-Difluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 464
carboxylic acid (1-benzyl-pyrrolidin-3-yl)-methyl-amide 1081
1-(4-Trifluoromethoxy-phenyl)-5-trifluoromethyl-1H- 512
pyrazole-4-carboxylic acid (1-benzyl-pyrrolidin-3-yl)- methyl-amide
1082 1-(3-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 450
carboxylic acid (5-diisopropylamino-pyrimidin-2-yl)- amide 1083
1-(3,4-Difluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 468
carboxylic acid (5-diisopropylamino-pyrimidin-2-yl)- amide 1084
1-(4-Trifluoromethoxy-phenyl)-5-trifluoromethyl-1H- 516
pyrazole-4-carboxylic acid (5-diisopropylamino-
pyrimidin-2-yl)-amide 1085
1-(3-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 428 carboxylic
acid (3-sulfamoyl-phenyl)-amide 1086
1-(3,4-Difluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 446
carboxylic acid (3-sulfamoyl-phenyl)-amide 1087
1-(4-Trifluoromethoxy-phenyl)-5-trifluoromethyl-1H- 494
pyrazole-4-carboxylic acid (3-sulfamoyl-phenyl)-amide 1088
1-(3,4-Difluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 443
carboxylic acid (2-chloro-pyrimidin-5-yl)-amide 1089
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 448 carboxylic
acid (3-thiazol-2-yl-phenyl)-amide
1090 1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 461
carboxylic acid [3-(3-methyl-5-oxo-4,5-dihydro-pyrazol-
1-yl)-phenyl]-amide 1091
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 482 carboxylic
acid (3-benzooxazol-2-yl-phenyl)-amide 1092
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 408 carboxylic
acid (3-carbamoyl-phenyl)-amide 1093
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 408 carboxylic
acid (3-dimethylamino-phenyl)-amide 1094
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 473 carboxylic
acid [3-(2-hydroxy-ethanesulfonyl)-phenyl]- amide 1095
4-{[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole- 472
4-carbonyl]-amino}-piperidine-1-carboxylic acid tert- butyl ester
1096 1-(3-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 429
carboxylic acid (2-methyl-5-phenyl-2H-pyrazol-3-yl)- amide 1097
(4-Benzyl-piperazin-1-yl)-[1-(3-fluoro-phenyl)-5- 432
trifluoromethyl-1H-pyrazol-4-yl]-methanone 1098
1-(3-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 350 carboxylic
acid pyridin-4-ylamide 1099 Biphenyl-3-carboxylic acid
(2-methyl-5-phenyl-2H- 353 pyrazol-3-yl)-amide 1100
Biphenyl-4-carboxylic acid (2-methyl-5-phenyl-2H- 353
pyrazol-3-yl)-amide 1101 4'-Chloro-biphenyl-3-carboxylic acid
(2-methyl-5-phenyl- 387 2H-pyrazol-3-yl)-amide 1102
3-{[1-(3-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 456
carbonyl]-amino}-piperidine-1-carboxylic acid tert-butyl ester 1103
1-(3,4-Difluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 447
carboxylic acid (2-methyl-5-phenyl-2H-pyrazol-3-yl)- amide 1104
(4-Benzyl-piperazin-1-yl)-[1-(3,4-difluoro-phenyl)-5- 450
trifluoromethyl-1H-pyrazol-4-yl]-methanone 1105
1-(3,4-Difluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 368
carboxylic acid pyridin-4-ylamide 1106
3-{[1-(3,4-Difluoro-phenyl)-5-trifluoromethyl-1H- 474
pyrazole-4-carbonyl]-amino}-piperidine-1-carboxylic acid tert-butyl
ester 1107 1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 514
carboxylic acid [3-(morpholine-4-sulfonyl)-phenyl]-amide 1108
1-(4-Trifluoromethoxy-phenyl)-5-trifluoromethyl-1H- 495
pyrazole-4-carboxylic acid (2-methyl-5-phenyl-2H-
pyrazol-3-yl)-amide 1109
1-(4-Trifluoromethoxy-phenyl)-5-trifluoromethyl-1H- 416
pyrazole-4-carboxylic acid pyridin-4-ylamide 1110
3-{[1-(4-Trifluoromethoxy-phenyl)-5-trifluoromethyl-1H- 522
pyrazole-4-carbonyl]-amino}-piperidine-1-carboxylic acid tert-butyl
ester 1111 Methanesulfonic acid 1-[1-(4-chloro-phenyl)-5- 451
trifluoromethyl-1H-pyrazole-4-carbonyl]-piperidin-4-yl ester 1112
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 458 carboxylic
acid (3-methylsulfamoyl-phenyl)-amide 1113
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 442 carboxylic
acid (3-pyridin-2-yl-phenyl)-amide 1114
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 442 carboxylic
acid (3-pyridin-3-yl-phenyl)-amide 1115
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 442 carboxylic
acid (3-pyridin-4-yl-phenyl)-amide 1116
1-(4-Fluoro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 428 carboxylic
acid (3-sulfamoyl-phenyl)-amide 1117
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 497 carboxylic
acid (3-trifluoromethanesulfonyl-phenyl)- amide 1118
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 458 carboxylic
acid (3-methanesulfonylamino-phenyl)-amide 1119
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 433 carboxylic
acid [3-(2H-tetrazol-5-yl)-phenyl]-amide 1120
[(3-{[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-
4-carbonyl]-amino}-phenyl)-imino-methyl]-carbamic acid tert-butyl
ester 1121 1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4-
carboxylic acid (3-carbamimidoyl-phenyl)-amide 1122
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 380 carboxylic
acid (3-amino-phenyl)-amide 1123
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- carboxylic
acid (3-ureido-phenyl)-amide 1127
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 444 carboxylic
acid (4-sulfamoyl-phenyl)-amide 1130
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 422 carboxylic
acid (3-acetylamino-phenyl)-amide 1131
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 484 carboxylic
acid (3-cyclopropylsulfamoyl-phenyl)-amide 1132
[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4-yl]- 449
(4-pyridin-2-ylmethyl-piperazin-1-yl)-methanone 1133
[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4-yl]- 449
(4-pyridin-3-ylmethyl-piperazin-1-yl)-methanone 1134
[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4-yl]- 449
(4-pyridin-4-ylmethyl-piperazin-1-yl)-methanone 1135
[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazol-4-yl]- 469
[4-(1-methyl-piperidin-3-ylmethyl)-piperazin-1-yl]- methanone 1136
2-Phenyl-2H-pyrazole-3-carboxylic acid pyridin-4- 264 ylamide 1137
(4-Benzyl-piperazin-1-yl)-(2-phenyl-2H-pyrazol-3-yl)- 346 methanone
1138 2-Phenyl-2H-pyrazole-3-carboxylic acid (3- 341
methanesulfonyl-phenyl)-amide 1139
2-Phenyl-2H-pyrazole-3-carboxylic acid (1H- 303
benzoimidazol-2-yl)-amide 1140 2-Phenyl-2H-pyrazole-3-carboxylic
acid 3- 345 trifluoromethyl-benzylamide 1141
2-Phenyl-2H-pyrazole-3-carboxylic acid (2-methyl-5- 343
phenyl-2H-pyrazol-3-yl)-amide 1142
2-Phenyl-2H-pyrazole-3-carboxylic acid (3-sulfamoyl- 342
phenyl)-amide 1143 2-Phenyl-2H-pyrazole-3-carboxylic acid
(1-benzyl- 360 piperidin-4-yl)-amide 1144
2-Phenyl-2H-pyrazole-3-carboxylic acid (1-benzyl- 346
pyrrolidin-3-yl)-amide 1145 2-Phenyl-2H-pyrazole-3-carboxylic acid
(1-benzyl- 346 pyrrolidin-3-yl)-amide 1146
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 411 carboxylic
acid (3-methylsulfanyl-phenyl)-amide 1147
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 427 carboxylic
acid (3-methanesulfinyl-phenyl)-amide 1148
3-{[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole- 445
4-carbonyl]-amino}-benzenesulfonic acid 1151
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 577 carboxylic
acid {3-[(methanesulfonylimino-phenoxy-
methyl)-amino]-phenyl}-amide 1152
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 500 carboxylic
acid {3-[(amino-methanesulfonylimino- methyl)-amino]-phenyl}-amide
1153 1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 514
carboxylic acid {3-[(methanesulfonylimino-methylamino-
methyl)-amino]-phenyl}-amide 1154
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 540 carboxylic
acid {3-[(cyclopropylamino-
methanesulfonylimino-methyl)-amino]-phenyl}-amide 1155
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 528 carboxylic
acid {3-[(dimethylamino-
methanesulfonylimino-methyl)-amino]-phenyl}-amide 1156
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 556 carboxylic
acid (3-{[(isopropyl-methyl-amino)-
methanesulfonylimino-methyl]-amino}-phenyl)-amide 1157
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 594 carboxylic
acid [3-(2,4-dimethoxy-benzylsulfamoyl)- phenyl]-amide 1158
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 555 carboxylic
acid [3-(2-piperidin-1-yl-ethylsulfamoyl)- phenyl]-amide 1159
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 557 carboxylic
acid [3-(3-diethylamino-propylsulfamoyl)- phenyl]-amide 1160
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 594 carboxylic
acid [3-(2,3-dimethoxy-benzylsulfamoyl)- phenyl]-amide 1161
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 569 carboxylic
acid {3-[3-(2-oxo-pyrrolidin-1-yl)- propylsulfamoyl]-phenyl}-amide
1162 1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 605
carboxylic acid {3-[2-(ethyl-m-tolyl-amino)-
ethylsulfamoyl]-phenyl}-amide 1163
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 514 carboxylic
acid [3-(3-hydroxy-pyrrolidine-1-sulfonyl)- phenyl]-amide 1164
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 500 carboxylic
acid (3-butylsulfamoyl-phenyl)-amide 1165
[3-(3-{[1-(4-Chloro-phenyl)-5-trifluoromethyl-1H- 601
pyrazole-4-carbonyl]-amino}-benzenesulfonylamino)- propyl]-carbamic
acid tert-butyl ester 1166
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 514 carboxylic
acid [3-(3-hydroxy-pyrrolidine-1-sulfonyl)- phenyl]-amide 1167
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 502 carboxylic
acid [3-(2-hydroxy-propylsulfamoyl)-phenyl]- amide 1168
(4-Benzyl-piperazin-1-yl)-[1-(4-chloro-phenyl)-5- 448
trifluoromethyl-1H-pyrazol-4-yl]-methanone 1169
(4-Benzyl-4-hydroxy-piperidin-1-yl)-[1-(4-chloro- 463
phenyl)-5-trifluoromethyl-1H-pyrazol-4-yl]-methanone 1170
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 555 carboxylic
acid {3-[(1-ethyl-pyrrolidin-2-ylmethyl)- sulfamoyl]-phenyl}-amide
1171 1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 543
carboxylic acid [3-(2-diethylamino-ethylsulfamoyl)- phenyl]-amide
1172 1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 563
carboxylic acid {3-[2-(4-amino-phenyl)-ethylsulfamoyl]-
phenyl}-amide 1173
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 541 carboxylic
acid [3-(2-pyrrolidin-1-yl-ethylsulfamoyl)- phenyl]-amide 1174
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 535 carboxylic
acid {3-[(pyridin-3-ylmethyl)-sulfamoyl]- phenyl}-amide 1175
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 515 carboxylic
acid [3-(2-dimethylamino-ethylsulfamoyl)- phenyl]-amide 1176
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 530 carboxylic
acid [3-(thiomorpholine-4-sulfonyl)-phenyl]- amide 1177
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 541 carboxylic
acid [3-(4-methyl-[1,4]diazepane-1-sulfonyl)- phenyl]-amide 1178
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 527 carboxylic
acid [3-(4-methyl-piperazine-1-sulfonyl)- phenyl]-amide 1179
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 582 carboxylic
acid {3-[2-(3-chloro-phenyl)-ethylsulfamoyl]-phenyl}- amide 1180
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 563 carboxylic
acid {3-[methyl-(2-pyridin-2-yl-ethyl)-sulfamoyl]- phenyl}-amide
1181 1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 472
carboxylic acid (3-ethylsulfamoyl-phenyl)-amide 1182
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 502 carboxylic
acid {3-[(2-hydroxy-ethyl)-methyl-sulfamoyl]-phenyl}- amide 1183
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 500 carboxylic
acid (3-diethylsulfamoyl-phenyl)-amide 1184
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 500 carboxylic
acid (6-methanesulfonyl-benzothiazol-2-yl)-amide 1185
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 458 carboxylic
acid (2-methyl-3-sulfamoyl-phenyl)-amide 1186
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 458 carboxylic
acid (2-sulfamoylmethyl-phenyl)-amide 1187
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 478 carboxylic
acid (2-chloro-5-sulfamoyl-phenyl)-amide 1188
1-(4-Chloro-phenyl)-5-trifluoromethyl-1H-pyrazole-4- 465 carboxylic
acid (4-methyl-5-sulfamoyl-thiazol-2-yl)-amide
[0161] It is understood that the examples and embodiments described
herein are for illustrative purposes only and that various
modifications or changes in light thereof will be suggested to
persons skilled in the art and are to included within the spirit
and purview of this application and are considered within the scope
of the appended claims. All publications, patents, and patent
applications cited herein are hereby incorporated by reference in
their entirety for all purposes.
* * * * *